95 results on '"Lindenmeyer M"'
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2. Vangl2, a planar cell polarity molecule, is implicated in irreversible and reversible kidney glomerular injury
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Papakrivopoulou, Eugenia, Vasilopoulou, E., Lindenmeyer, M., Pacheco, Sabrina, Brzoska, Hortensja L., Price, Karen L., Kolatsi-Joannou, Maria, White, Kathryn E., Henderson, Deborah J., Dean, Charlotte H., Cohen, Clemens D., Salama, Alan D., Woolf, Adrian S., and Long, David A.
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Adult ,Male ,matrix metalloproteinase ,podocyte ,kidney disease ,Kidney Glomerulus ,glomerulus ,planar cell polarity ,Nerve Tissue Proteins ,urologic and male genital diseases ,Young Adult ,Animals ,Humans ,Cells, Cultured ,Mice, Knockout ,Original Paper ,urogenital system ,Glomerulosclerosis, Focal Segmental ,Podocytes ,Nephrosis, Lipoid ,Intracellular Signaling Peptides and Proteins ,Cell Polarity ,Membrane Proteins ,Middle Aged ,Original Papers ,QR ,Enzyme Activation ,Mice, Inbred C57BL ,Disease Models, Animal ,Matrix Metalloproteinase 9 ,Case-Control Studies ,Female ,Signal Transduction - Abstract
Planar cell polarity (PCP) pathways control the orientation and alignment of epithelial cells within tissues. Van Gogh‐like 2 (Vangl2) is a key PCP protein that is required for the normal differentiation of kidney glomeruli and tubules. Vangl2 has also been implicated in modifying the course of acquired glomerular disease, and here, we further explored how Vangl2 impacts on glomerular pathobiology in this context. Targeted genetic deletion of Vangl2 in mouse glomerular epithelial podocytes enhanced the severity of not only irreversible accelerated nephrotoxic nephritis but also lipopolysaccharide‐induced reversible glomerular damage. In each proteinuric model, genetic deletion of Vangl2 in podocytes was associated with an increased ratio of active‐MMP9 to inactive MMP9, an enzyme involved in tissue remodelling. In addition, by interrogating microarray data from two cohorts of renal patients, we report increased VANGL2 transcript levels in the glomeruli of individuals with focal segmental glomerulosclerosis, suggesting that the molecule may also be involved in certain human glomerular diseases. These observations support the conclusion that Vangl2 modulates glomerular injury, at least in part by acting as a brake on MMP9, a potentially harmful endogenous enzyme. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
- Published
- 2018
3. Genetic Background but Not Intestinal Microbiota After Co-Housing Determines Hyperoxaluria-Related Nephrocalcinosis in Common Inbred Mouse Strains
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Ma, Q., Grigorescu, M., Schreiber, A., Kettritz, R., Lindenmeyer, M., Anders, H.J., and Steiger, S.
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Mice, Knockout ,Hyperoxaluria ,Calcium Oxalate ,uromodulin ,Immunology ,kidney stone disease ,Housing, Animal ,Gastrointestinal Microbiome ,mouse strains ,Disease Models, Animal ,Mice ,Nephrocalcinosis ,Cardiovascular and Metabolic Diseases ,microbiota ,Animals ,Immunology and Allergy ,Original Research - Abstract
Calcium oxalate (CaOx) crystal formation, aggregation and growth is a common cause of kidney stone disease and nephrocalcinosis-related chronic kidney disease (CKD). Genetically modified mouse strains are frequently used as an experimental tool in this context but observed phenotypes may also relate to the genetic background or intestinal microbiota. We hypothesized that the genetic background or intestinal microbiota of mice determine CaOx crystal deposition and thus the outcome of nephrocalcinosis. Indeed, Casp1(-/-), Cybb(-/-) or Casp1(-/-)/Cybb(-/-) knockout mice on a 129/C57BL/6J (B6J) background that were fed an oxalate-rich diet for 14 days did neither encounter intrarenal CaOx crystal deposits nor nephrocalcinosis-related CKD. To test our assumption, we fed C57BL/6N (B6N), 129, B6J and Balb/c mice an oxalate-rich diet for 14 days. Only B6N mice displayed CaOx crystal deposits and developed CKD associated with tubular injury, inflammation and interstitial fibrosis. Intrarenal mRNA expression profiling of 64 known nephrocalcinosis-related genes revealed that healthy B6N mice had lower mRNA levels of uromodulin (Umod) compared to the other three strains. Feeding an oxalate-rich diet caused an increase in uromodulin protein expression and CaOx crystal deposition in the kidney as well as in urinary uromodulin excretion in B6N mice but not 129, B6J and Balb/c mice. However, backcrossing 129 mice on a B6N background resulted in a gradual increase in CaOx crystal deposits from F2 to F7, of which all B6N/129 mice from the 7th generation developed CaOx-related nephropathy similar to B6N mice. Co-housing experiments tested for a putative role of the intestinal microbiota but B6N co-housed with 129 mice or B6N/129 (3rd and 6th generation) mice did not affect nephrocalcinosis. In summary, genetic background but not the intestinal microbiome account for strain-specific crystal formation and, the levels of uromodulin secretion may contribute to this phenomenon. Our results imply that only littermate controls of the identical genetic background strain are appropriate when performing knockout mouse studies in this context, while co-housing is optional.
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- 2021
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4. Wnt Pathway Regulation in Chronic Renal Allograft Damage
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von Toerne, C., Schmidt, C., Adams, J., Kiss, E., Bedke, J., Porubsky, S., Gretz, N., Lindenmeyer, M. T., Cohen, C. D., Gröne, H.-J., and Nelson, P. J.
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- 2009
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5. Collagen type VIII expression in human diabetic nephropathy
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Gerth, J., Cohen, C. D., Hopfer, U., Lindenmeyer, M. T., Sommer, M., Gröne, H. J., and Wolf, G.
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- 2007
6. Microarray analysis reveals influence of the sesquiterpene lactone parthenolide on gene transcription profiles in human epithelial cells
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Lindenmeyer, M. T., Kern, C., Sparna, T., Donauer, J., Wilpert, J., Schwager, J., Porath, D., Kreutz, C., Timmer, J., and Merfort, I.
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- 2007
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7. Vangl2, a planar cell polarity molecule, is implicated in irreversible and reversible kidney glomerular injury
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Dean, C, Papakrivopoulou, E, Vasilopoulou, E, Lindenmeyer, M, Pacheco, S, Brzoska, H, Price, K, Kolatsi-Joannou, M, White, K, Henderson, D, Cohen, C, Salama, A, and Woolf, A
- Subjects
urogenital system ,Pathology ,1103 Clinical Sciences ,urologic and male genital diseases - Abstract
Planar cell polarity (PCP) pathways control the orientation and alignment of epithelial cells within tissues. Van Gogh‐like 2 (Vangl2) is a key PCP protein that is required for normal differentiation of kidney glomeruli and tubules. Vangl2 has also been implicated in modifying the course of acquired glomerular disease and here we further explored how Vangl2 impacts on glomerular pathobiology in this context. Targeted genetic deletion of Vangl2 in mouse glomerular epithelial podocytes enhanced the severity of not only irreversible accelerated nephrotoxic nephritis but also lipopolysaccharide‐induced reversible glomerular damage. In each proteinuric model, genetic deletion of Vangl2 in podocytes was associated with an increased ratio of active‐MMP9 to inactive MMP9, an enzyme involved in tissue remodelling. Additionally, by interrogating microarray data from two cohorts of renal patients, we report increased VANGL2 transcript levels in glomeruli of individuals with focal segmental glomerulosclerosis, suggesting that the molecule may also be involved in certain human glomerular diseases. These observations support the conclusion that Vangl2 modulates glomerular injury, at least in part by acting as a brake on MMP9, a potentially harmful endogenous enzyme.
- Published
- 2018
8. New sesquiterpene lactones from Arnica tincture prepared from fresh flowerheads of Arnica montana
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Kos, O., Lindenmeyer, M. T., Tubaro, Aurelia, Sosa, Silvio, Merfort, I., Kos, O., Lindenmeyer, M. T., Tubaro, Aurelia, Sosa, Silvio, and Merfort, I.
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Anti-inflammatory activity ,Arnia montana ,Asteraceae - Published
- 2005
9. Genexpressionsanalysen von FSGS- und MCD-Nierenbiopsien identifizieren eine klinische Subgruppe mit spezifischem TNF-alpha-mRNA-Profil
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Martini, S., primary, Nair, V., additional, Eichinger, F., additional, Reich, H., additional, Lindenmeyer, M., additional, Kretzler, M., additional, and (NEPTUNE), Nephrotic Syndrome Study Network, additional
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- 2015
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10. Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC inflammasome-mediated activation of caspase-1
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Lichtnekert, J, Kulkarni, O P, Mulay, S R, Rupanagudi, K V, Ryu, M, Allam, R, Vielhauer, V, Muruve, D, Lindenmeyer, M T, Cohen, C D, Anders, H J, and University of Zurich
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1000 Multidisciplinary ,1300 General Biochemistry, Genetics and Molecular Biology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,1100 General Agricultural and Biological Sciences ,10052 Institute of Physiology - Published
- 2011
11. Human nephrosclerosis triggers a hypoxia-related glomerulopathy
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Neusser, M A, Lindenmeyer, M T, Moll, A G, Segerer, S, Edenhofer, I, Sen, K, Stiehl, D P, Kretzler, M, Gröne, H J, Schlöndorff, D, Cohen, C D, and University of Zurich
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2734 Pathology and Forensic Medicine ,10076 Center for Integrative Human Physiology ,570 Life sciences ,biology ,610 Medicine & health ,10029 Clinic and Policlinic for Internal Medicine ,10052 Institute of Physiology - Published
- 2010
12. Renal tubular PD-L1 (CD274) suppresses alloreactive human T-cell responses
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Starke, A, Lindenmeyer, M T, Segerer, S, Neusser, M A, Rüsi, B, Schmid, D M, Cohen, C D, Wüthrich, R P, Fehr, T, Waeckerle-Men, Y, University of Zurich, and Fehr, T
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10062 Urological Clinic ,2727 Nephrology ,10076 Center for Integrative Human Physiology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,10052 Institute of Physiology - Published
- 2010
13. Patients with IgA nephropathy exhibit high systemic PDGF-DD levels
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Boor, P, Eitner, F, Cohen, C D, Lindenmeyer, M T, Mertens, P R, Ostendorff, T, Floege, J, University of Zurich, and Boor, P
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2727 Nephrology ,2747 Transplantation ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,10052 Institute of Physiology - Published
- 2009
14. Transcript-specific expression profiles derived from sequence-based analysis of standard microarrays
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Moll, A G, Lindenmeyer, M T, Kretzler, M, Nelson, P J, Zimmer, R, Cohen, C D, University of Zurich, and Moll, A G
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1000 Multidisciplinary ,1300 General Biochemistry, Genetics and Molecular Biology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,1100 General Agricultural and Biological Sciences ,10052 Institute of Physiology - Published
- 2009
15. Alterations of the podocyte proteome in response to high glucose concentrations
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Schordan, S, Schordan, E, Lindenmeyer, M T, Cohen, C D, Endlich, K, Maurer, M, University of Zurich, and Endlich, K
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1303 Biochemistry ,1312 Molecular Biology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,10052 Institute of Physiology - Published
- 2009
16. Genomic Analysis in Nephrology – towards Systems Biology and Systematic Medicine?
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Neusser, M A, Lindenmeyer, M T, Kretzler, M, Cohen, C D, University of Zurich, and Cohen, C D
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2727 Nephrology ,10076 Center for Integrative Human Physiology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,10052 Institute of Physiology - Published
- 2008
17. Proteinuria and hyperglycemia induce endoplasmic reticulum stress
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Lindenmeyer, M T, Rastaldi, M P, Ikehata, M, Neusser, M A, Kretzler, M, Cohen, C D, Schlöndorff, D, and University of Zurich
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2727 Nephrology ,10076 Center for Integrative Human Physiology ,570 Life sciences ,biology ,610 Medicine & health ,10035 Clinic for Nephrology ,10052 Institute of Physiology - Published
- 2008
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18. 25. Ergebnisse des geburtshilflich-neonatologischen Dienstes am Kantonsspital Aarau der Jahre 1982–1984 bezüglich Kinder der Gewichtsklasse unter 2500 g
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Lefani, A., Lindenmeyer, M., and Harder, M.
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- 1986
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19. PATHOLOGY INFLAMMATION
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Maciel, T. T., primary, Merle, E., additional, Fricot, A., additional, Monteiro, R., additional, Moura, I. C., additional, Seleznik, G., additional, Seeger, H., additional, Papandile, A., additional, Fu, K., additional, Poreci, U., additional, Czerkowicz, J., additional, Rabah, D., additional, Ranger, A., additional, Cohen, C. D., additional, Lindenmeyer, M., additional, Chen, J., additional, Edenhofer, I., additional, Anders, H.-J., additional, Lech, M., additional, Wuthrich, R. P., additional, Ruddle, N. H., additional, Moeller, M. J., additional, Regele, H., additional, Kozakowski, N., additional, Bauer, J., additional, Heikenwalder, M., additional, Browning, J. L., additional, Segerer, S., additional, Kirsch, A. H., additional, Artinger, K., additional, Rho, E., additional, Wolf, A. M., additional, Cornez, I., additional, Eller, P., additional, Wolf, D., additional, Rosenkranz, A. R., additional, Eller, K., additional, Schaubettl, C., additional, Aringer, I., additional, Grande, J. P., additional, Hartono, S. P., additional, Kashyap, S., additional, and Knudsen, B., additional
- Published
- 2014
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20. Expression of the chemokine receptor CCR6 in human renal inflammation
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Welsh-Bacic, D, Lindenmeyer, M, Cohen, C D, Draganovici, D, Mandelbaum, J, Edenhofer, I, Ziegler, U, Regele, H, Wüthrich, R P, Segerer, S, Welsh-Bacic, D, Lindenmeyer, M, Cohen, C D, Draganovici, D, Mandelbaum, J, Edenhofer, I, Ziegler, U, Regele, H, Wüthrich, R P, and Segerer, S
- Abstract
BACKGROUND: Nodular inflammatory cell infiltrates with defined microarchitecture, i.e. tertiary lymphoid organs, develop in the tubulointerstitium during chronic renal inflammation. CCR6 and the corresponding ligand CCL20 are involved in the formation of gut-associated lymphatic tissue. We hypothesized that CCR6 might be involved in the formation of nodular infiltrates in the kidney. METHODS: CCR6- and CD20-positive B cells were localized in renal biopsies with IgA nephropathy (n = 13), membranous nephropathy (n = 12), crescentic glomerulonephritis (cGN, n = 11) and chronic interstitial nephritis (n = 13), and in pre-implantation biopsies as controls (n = 8). The mRNA expression of CCR6 and the ligand CCL20 was quantified by real-time RT-PCR in 51 renal biopsies of the same disease entities. RESULTS: In the pre-transplant biopsies, CCR6 was expressed by endothelial cells of peritubular and glomerular capillaries. In patients with glomerulonephritis, infiltrating cells were positive particularly in areas of nodular inflammatory cell accumulations. A major part of the CCR6-positive cells were CD20-positive B cells, but a part of the CD3-positive T cells were also found to be positive. The constitutive expression of CCR6 on the endothelium of glomerular capillaries was lost in biopsies with progressive injury. Tubular epithelial cells expressed CCR6 in inflamed kidneys, most commonly on the basolateral side. CONCLUSIONS: CCR6 and the corresponding ligand CCL20 might therefore be involved in the recruitment of T and B cells to organized nodular infiltrates in chronic renal inflammation. The functional role of endothelial CCR6 needs to be evaluated in further studies.
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- 2011
21. Dendritic cells in experimental renal inflammation - Part I
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Lindenmeyer, M, Noessner, E, Nelson, P J, Segerer, S, Lindenmeyer, M, Noessner, E, Nelson, P J, and Segerer, S
- Abstract
Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. While descriptions of cells with dendritic morphology in rodent kidneys date back to the early 1970s, a network of DCs in the mouse kidney has only recently been described. DCs acquire distinct phenotypic and functional characteristics depending on the microenvironment and the disease stages. Concomitantly, their communication with cells of the adaptive immunity might have tissue-protective or tissue-deleterious consequences. This review summarizes results from recent studies on the role of DCs in experimental renal inflammation. Copyright © 2011 S. Karger AG, Basel.
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- 2011
22. Dendritic cells in human renal inflammation - Part II
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Noessner, E, Lindenmeyer, M, Nelson, P J, Segerer, S, Noessner, E, Lindenmeyer, M, Nelson, P J, and Segerer, S
- Abstract
Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. Here, we review the available information on their role in human renal inflammation. In the 1980s and early 1990s, major histocompatibility complex class II antigen- (HLA-DR) positive DCs were first described in normal human kidneys and in the interstitium of kidneys from patients with glomerulonephritis. Several DC subtypes were subsequently distinguished based on their expression of CD1c/BDCA-1, CD141/BDCA-3 and CD209/DC-SIGN (in combination with HLA-DR). These cells were almost exclusively found in the tubulointerstitium, with increased numbers seen during glomerulonephritis. It appears that the human renal tubulointerstitium harbors different DC types which allow the collection of both exogenous as well as endogenous antigens. Plasmacytoid DCs have a plasma cell-like morphology and were commonly found within nodular tubulointerstitial infiltrates. Follicular DCs are rarely seen, but show a predominant localization in organized infiltrates. CD207/langerin is a marker for Langerhans cells. Langerin-positive cells have been found in association with the collecting ducts and urothelium. A functional characterization of these subtypes has been hampered by the difficulty of obtaining samples for analysis. However, these studies are clearly required to define the role of DCs and DC subsets in the pathophysiology of renal disease.
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- 2011
23. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice
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Gödel, M, Hartleben, B, Herbach, N, Liu, S, Zschiedrich, S, Lu, S, Debreczeni-Mór, A, Lindenmeyer, M T, Rastaldi, M P, Hartleben, G, Wiech, T, Fornoni, A, Nelson, R G, Kretzler, M, Wanke, R, Pavenstädt, H, Kerjaschki, D, Cohen, C D, Hall, M N, Rüegg, M A, Inoki, K, Walz, G, Huber, T B, Gödel, M, Hartleben, B, Herbach, N, Liu, S, Zschiedrich, S, Lu, S, Debreczeni-Mór, A, Lindenmeyer, M T, Rastaldi, M P, Hartleben, G, Wiech, T, Fornoni, A, Nelson, R G, Kretzler, M, Wanke, R, Pavenstädt, H, Kerjaschki, D, Cohen, C D, Hall, M N, Rüegg, M A, Inoki, K, Walz, G, and Huber, T B
- Abstract
Chronic glomerular diseases, associated with renal failure and cardiovascular morbidity, represent a major health issue. However, they remain poorly understood. Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis. Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis. In contrast, increased mTOR activity accompanied human diabetic nephropathy, characterized by early glomerular hypertrophy and hyperfiltration. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes prevented glomerulosclerosis and significantly ameliorated the progression of glomerular disease in diabetic nephropathy. These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy.
- Published
- 2011
24. Intrarenal production of B cell survival factors in human lupus nephritis
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Neusser, M A, Lindenmeyer, M T, Edenhofer, I, Gaiser, S, Kretzler, M, Regele, H, Segerer, S, Cohen, C D, Neusser, M A, Lindenmeyer, M T, Edenhofer, I, Gaiser, S, Kretzler, M, Regele, H, Segerer, S, and Cohen, C D
- Published
- 2011
25. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice
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Hartleben, B, Gödel, M, Meyer-Schwesinger, C, Liu, S, Ulrich, T, Köbler, S, Wiech, T, Grahammer, F, Arnold, S J, Lindenmeyer, M T, Cohen, C D, Pavenstädt, H, Kerjaschki, D, Mizushima, N, Shaw, A S, Walz, G, Huber, T B, Hartleben, B, Gödel, M, Meyer-Schwesinger, C, Liu, S, Ulrich, T, Köbler, S, Wiech, T, Grahammer, F, Arnold, S J, Lindenmeyer, M T, Cohen, C D, Pavenstädt, H, Kerjaschki, D, Mizushima, N, Shaw, A S, Walz, G, and Huber, T B
- Abstract
Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. These findings highlight the importance of induced autophagy as a key homeostatic mechanism to maintain podocyte integrity. We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function.
- Published
- 2010
26. Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset
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Lindenmeyer, M T, Eichinger, F, Sen, K, Anders, Hans-Joachim, Edenhofer, I, Mattinzoli, D, Kretzler, M, Rastaldi, M P, Cohen, C D, Lindenmeyer, M T, Eichinger, F, Sen, K, Anders, Hans-Joachim, Edenhofer, I, Mattinzoli, D, Kretzler, M, Rastaldi, M P, and Cohen, C D
- Abstract
Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease.
- Published
- 2010
27. Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis
- Author
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Cohen, C D, Lindenmeyer, M T, Eichinger, F, Hahn, A, Seifert, M, Moll, A G, Schmid, H, Kiss, E, Gröne, E, Gröne, H J, Kretzler, M, Werner, T, Nelson, P J, Cohen, C D, Lindenmeyer, M T, Eichinger, F, Hahn, A, Seifert, M, Moll, A G, Schmid, H, Kiss, E, Gröne, E, Gröne, H J, Kretzler, M, Werner, T, and Nelson, P J
- Abstract
Background: Diabetic nephropathy (DN) is a complex and chronic metabolic disease that evolves into a progressive fibrosing renal disorder. Effective transcriptomic profiling of slowly evolving disease processes such as DN can be problematic. The changes that occur are often subtle and can escape detection by conventional oligonucleotide DNA array analyses. Methodology/Principal Findings: We examined microdissected human renal tissue with or without DN using Affymetrix oligonucleotide microarrays (HG-U133A) by standard Robust Multi-array Analysis (RMA). Subsequent gene ontology analysis by Database for Annotation, Visualization and Integrated Discovery (DAVID) showed limited detection of biological processes previously identified as central mechanisms in the development of DN (e.g. inflammation and angiogenesis). This apparent lack of sensitivity may be associated with the gene-oriented averaging of oligonucleotide probe signals, as this includes signals from cross-hybridizing probes and gene annotation that is based on out of date genomic data. We then examined the same CEL file data using a different methodology to determine how well it could correlate transcriptomic data with observed biology. ChipInspector (CI) is based on single probe analysis and de novo gene annotation that bypasses probe set definitions. Both methods, RMA and CI, used at default settings yielded comparable numbers of differentially regulated genes. However, when verified by RT-PCR, the single probe based analysis demonstrated reduced background noise with enhanced sensitivity and fewer false positives. Conclusions/Significance: Using a single probe based analysis approach with de novo gene annotation allowed an improved representation of the biological processes linked to the development and progression of DN. The improved analysis was exemplified by the detection of Wnt signaling pathway activation in DN, a process not previously reported to be involved in this disease.
- Published
- 2008
28. Peritoneal dialysis - A
- Author
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Ito, M., primary, Emami-Naini, A., additional, Keyvandarian, N., additional, Moeinzadeh, F., additional, Mortazavi, M., additional, Taheri, S., additional, Io, K., additional, Nishino, T., additional, Obata, Y., additional, Kitamura, M., additional, Abe, S., additional, Koji, T., additional, Kohno, S., additional, Wakabayashi, K., additional, Hamada, C., additional, Nakano, T., additional, Kanda, R., additional, Io, H., additional, Horikoshi, S., additional, Tomino, Y., additional, Korte, M. R., additional, Braun, N., additional, Habib, S. M., additional, Goffin, E., additional, Summers, A., additional, Heuveling, L., additional, Betjes, M. G. H., additional, Lambie, M., additional, Bankart, J., additional, Johnson, D., additional, Mactier, R., additional, Phillips-Darby, L., additional, Topley, N., additional, Davies, S., additional, Liu, F. X., additional, Leipold, R., additional, Arici, M., additional, Farooqui, U., additional, Cho, K.-h., additional, Do, J.-y., additional, Kang, S.-h., additional, Park, J.-W., additional, Yoon, K.-W., additional, Jung, S.-Y., additional, Sise, C., additional, Rutherford, P., additional, Kovacs, L., additional, Konings, S., additional, Pestana, M., additional, Zimmermann, J., additional, Cramp, H., additional, Stein, D., additional, Bang, K., additional, Shin, J. H., additional, Jeong, J., additional, Kim, J.-H., additional, Matsuo, N., additional, Maruyama, Y., additional, Nakao, M., additional, Tanno, Y., additional, Ohkido, I., additional, Hayakawa, H., additional, Yamamoto, H., additional, Yokoyama, K., additional, Hosoya, T., additional, Iannuzzella, F., additional, Corradini, M., additional, Belloni, L., additional, Stefani, A., additional, Parmeggiani, M., additional, Pasquali, S., additional, Svedberg, O., additional, Stenvinkel, P., additional, Qureshi, A. R., additional, Barany, P., additional, Heimburger, O., additional, Leurs, P., additional, Anderstam, B., additional, Waniewski, J., additional, Antosiewicz, S., additional, Baczynski, D., additional, Galach, M., additional, Wankowicz, Z., additional, Prabhu, M., additional, Subhramanyam, S. V., additional, Nayak, K. S., additional, Hwang, J.-C., additional, Jiang, M.-Y., additional, Lu, Y.-H., additional, Wang, C.-T., additional, Santos, C., additional, Rodriguez-Carmona, A., additional, Perez Fontan, M., additional, Schaefer, B., additional, Macher-Goeppinger, S., additional, Bayazit, A., additional, Sallay, P., additional, Testa, S., additional, Holland-Cunz, S., additional, Querfeld, U., additional, Warady, B. A., additional, Schaefer, F., additional, Schmitt, C. P., additional, Guney, I., additional, Turkmen, K., additional, Yazici, R., additional, Aslan, S., additional, Altintepe, L., additional, Yeksan, M., additional, Kocyigit, I., additional, Sipahioglu, M., additional, Orscelik, O., additional, Unal, A., additional, Celik, A., additional, Abbas, S., additional, Zhu, F., additional, Tokgoz, B., additional, Dogan, A., additional, Oymak, O., additional, Kotanko, P., additional, Levin, N., additional, Sanchez-Gonzalez, M. C., additional, Gonzalez-Casaus, M. L., additional, Gonzalez-Parra, E., additional, Albalate, M., additional, Lorenzo, V., additional, Torregrosa, V., additional, Fernandez, E., additional, de la Piedra, C., additional, Rodriguez, M., additional, Zeiler, M., additional, Monteburini, T., additional, Agostinelli, R. M., additional, Marinelli, R., additional, Santarelli, S., additional, Bermond, F., additional, Bagnis, C., additional, Marcuccio, C., additional, Soragna, G., additional, Bruno, M., additional, Vitale, C., additional, Marangella, M., additional, Martino, F., additional, Scalzotto, E., additional, Rodighiero, M. P., additional, Crepaldi, C., additional, Ronco, C., additional, Seferi, S., additional, Rroji, M., additional, Likaj, E., additional, Barbullushi, M., additional, Thereska, N., additional, Kim, E. J., additional, Han, J. H., additional, Koo, H. M., additional, Doh, F. M., additional, Kim, C. H., additional, Ko, K. I., additional, Lee, M. J., additional, Oh, H. J., additional, Han, S. H., additional, Yoo, T.-H., additional, Choi, K. H., additional, Kang, S.-W., additional, Uzun, S., additional, Karadag, S., additional, Yegen, M., additional, Gursu, M., additional, Ozturk, S., additional, Aydin, Z., additional, Sumnu, A., additional, Cebeci, E., additional, Atalay, E., additional, Kazancioglu, R., additional, Alscher, D., additional, Fritz, P., additional, Latus, J., additional, Kimmel, M., additional, Biegger, D., additional, Lindenmeyer, M., additional, Cohen, C. D., additional, Wuthrich, R. P., additional, Segerer, S., additional, Kim, Y. K., additional, Kim, H. W., additional, Song, H. C., additional, Choi, E. J., additional, Yang, C. W., additional, Matsuda, A., additional, Tayama, Y., additional, Ogawa, T., additional, Iwanaga, M., additional, Okazaki, S., additional, Hatano, M., additional, Kiba, T., additional, Shimizu, T., additional, Hasegawa, H., additional, Mitarai, T., additional, Dratwa, M., additional, Collart, F., additional, Verger, C., additional, Takayanagi, K., additional, Iwashita, T., additional, Noiri, C., additional, Inamura, M., additional, Nakamura, S., additional, Kato, H., additional, Sipahioglu, M. H., additional, Elmali, F., additional, Zhang, X., additional, Ma, J., additional, Giuliani, A., additional, Blanca-Martos, L., additional, Nayak Karopadi, A., additional, Mason, G., additional, Santos, M. T., additional, Fonseca, I., additional, Santos, O., additional, Rocha, M. J., additional, Carvalho, M. J., additional, Cabrita, A., additional, Rodrigues, A., additional, Scabbia, L., additional, Domenici, A., additional, Apponi, F., additional, Tayefeh Jafari, M., additional, Sivo, F., additional, Falcone, C., additional, Punzo, G., additional, Mene, P., additional, Yildirim, T., additional, Yilmaz, R., additional, Azak, A., additional, Altindal, M., additional, Turkmen, E., additional, Altun, B., additional, Duranay, M., additional, Erdem, Y., additional, Buyukbakkal, M., additional, Eser, B., additional, Yayar, O., additional, Ercan, Z., additional, Kali, A., additional, Erdogan, B., additional, Haspulat, A., additional, Merhametsiz, O., additional, Ulusal-Okyay, G., additional, Akdag, S. I., additional, Ayli, M. D., additional, Pietrzycka, A., additional, Miarka, P., additional, Chowaniec, E., additional, Sulowicz, W., additional, Lutwin, M., additional, Gaska, M., additional, and Paciorek, A., additional
- Published
- 2013
- Full Text
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29. The SVX II silicon vertex detector upgrade at CDF
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Antos, J., Chao, H. Y., Chang, P., Cheng, M. T., Chu, M. L., Guo, R. S., C. L., Ho, Teng, P. K., Wang, M. J., S. C., Wu, Yeh, G. P., Yeh, P., Andressen, J., Barsotti, E., Bowden, M., Cihangir, S., Gonzalez, H., Grimm, C., Haynes, B., Hrycyk, M., Howell, J., Husby, D., Knopf, W., Lindenmeyer, M., Ratzmann, P., Sarge, J., Spalding, J., Spiegel, L., Tkaczyk, S., Woodbury, K., Yarema, R., Zimmerman, S., Zimmerman, T., Gay, C., Huth, J., Oliver, J., Spiropulu, M., Stroehmer, R., Iwata, Y., Ohmoto, T., Ohsugi, T., Barnett, B., Skarha, J., Snider, R., Takashima, R., Ely, R., Garciasciveres, M., Haber, C., Milgrome, O., Lu, L., Bailey, M., Bruner, N., Gold, M., Hoeferkamp, M., Matthews, J., Moore, E., Seidel, S., Thomas, T., Worm, S., Yu, L., Kohriki, T., Unno, Y., Tamura, N., Bacchetta, N., Bisello, Dario, Bolla, G., Boudreau, J., Engels, E., Huffman, B. T., Shepard, P. F., Rosatti, R., Bedeschi, F., Menzione, A., Punzi, G., Ristori, L., Zetti, F., Bortoletto, D., Garfinkel, A., Hardmann, A., Hoffman, K., Keaffaber, T., Shaw, N. M., Cassada, J., Tipton, P., Conway, J., Done, J., Kamon, T., Tannenbaum, B., Wolinski, J., Benjamin, D., Frautschi, M., Sill, A., and Hou, J. F.
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Nuclear and High Energy Physics ,Instrumentation - Published
- 1996
30. Resistance to ABT-737 in activated T lymphocytes: molecular mechanisms and reversibility by inhibition of the calcineurin–NFAT pathway
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Cippà, P E, primary, Kraus, A K, additional, Lindenmeyer, M T, additional, Chen, J, additional, Guimezanes, A, additional, Bardwell, P D, additional, Wekerle, T, additional, Wüthrich, R P, additional, and Fehr, T, additional
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- 2012
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31. Expression of the chemokine receptor CCR6 in human renal inflammation
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Welsh-Bacic, D., primary, Lindenmeyer, M., additional, Cohen, C. D., additional, Draganovici, D., additional, Mandelbaum, J., additional, Edenhofer, I., additional, Ziegler, U., additional, Regele, H., additional, Wuthrich, R. P., additional, and Segerer, S., additional
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- 2010
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32. Aerobic synthesis of vitamin B12: ring contraction and cobalt chelation
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Heldt, D., primary, Lawrence, A.D., additional, Lindenmeyer, M., additional, Deery, E., additional, Heathcote, P., additional, Rigby, S.E., additional, and Warren, M.J., additional
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- 2005
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33. A flexible front-end electronics hybrid for silicon microstrip detectors
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Iwata, Y., primary, Ohsugi, T., additional, Ohmoto, T., additional, Handa, T., additional, Sato, K., additional, Yamamoto, H., additional, Takashima, R., additional, Kondo, T., additional, Unno, Y., additional, Terada, S., additional, Kohriki, T., additional, Nakano, I., additional, Lindenmeyer, M., additional, Tkaczyk, S., additional, Erdmann, W., additional, Spalding, J., additional, Dychakowski, G., additional, Bolla, G., additional, Pope, G., additional, and Shepard, P., additional
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- 2001
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34. The SVX II silicon vertex detector upgrade at CDF
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Antos, J., primary, Chao, H-Y., additional, Chang, P., additional, Cheng, M-T., additional, Chu, M-L., additional, Guo, R-S., additional, Ho, C-L., additional, Teng, P-K., additional, Wang, M-J., additional, Wu, S-C., additional, Yeh, G-P, additional, Yeh, P., additional, Andressen, J., additional, Barsotti, E., additional, Bowden, M., additional, Cihangir, S., additional, Gonzalez, H., additional, Grimm, C., additional, Haynes, B., additional, Hrycyk, M., additional, Howell, J., additional, Husby, D., additional, Knopf, W., additional, Lindenmeyer, M., additional, Ratzmann, P., additional, Sarge, J., additional, Spalding, J., additional, Spiegel, L., additional, Tkaczyk, S., additional, Woodbury, K., additional, Yarema, R., additional, Zimmerman, S., additional, Zimmerman, T., additional, Gay, C., additional, Huth, J., additional, Oliver, J., additional, Spiropulu, M., additional, Stroehmer, R., additional, Iwata, Y., additional, Ohmoto, T., additional, Ohsugi, T., additional, Barnett, B., additional, Skarha, J., additional, Snider, R., additional, Takashima, R., additional, Ely, R., additional, Garcia-Sciveres, M., additional, Haber, C., additional, Milgrome, O., additional, Lu, L., additional, Bailey, M., additional, Bruner, N., additional, Gold, M., additional, Hoeferkamp, M., additional, Matthews, J., additional, Moore, E., additional, Seidel, S., additional, Thomas, T., additional, Worm, S., additional, Yu, L., additional, Kohriki, T., additional, Unno, Y., additional, Tamura, N., additional, Bacchetta, N., additional, Bisello, D., additional, Bolla, G., additional, Boudreau, J., additional, Engels, E., additional, Huffman, B.T., additional, Shepard, P.F., additional, Rosatti, R., additional, Bedeschi, F., additional, Menzione, A., additional, Punzi, G., additional, Ristori, L., additional, Zetti, F., additional, Bortoletto, D., additional, Garfinkel, A., additional, Hardmann, A., additional, Hoffman, K., additional, Keaffaber, T., additional, Shaw, N.M., additional, Cassada, J., additional, Tipton, P., additional, Conway, J., additional, Done, J., additional, Kamon, T., additional, Tannenbaum, B., additional, Wolinski, J., additional, Benjamin, D., additional, Frautschi, M., additional, Sill, A., additional, and Hou, J-F., additional
- Published
- 1996
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35. The SVX II silicon vertex detector upgrade at CDF
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Antos, J., primary, Chao, H-Y., additional, Cheng, M-T., additional, Chu, M-L., additional, Guo, R-S., additional, Ho, C-L., additional, Teng, P-K., additional, Wang, M-J., additional, Wu, S-C., additional, Yeh, G-P., additional, Yeh, P., additional, Blucher, E., additional, Frisch, H., additional, Sullivan, G., additional, Barsotti, E., additional, Cihangir, S., additional, Gonzalez, H., additional, Hrycyk, M., additional, Lindenmeyer, M., additional, Pawlak, J., additional, Ratzmann, P., additional, Spalding, J., additional, Spiegel, L., additional, Swoboda, C., additional, Yarema, R., additional, Zimmerman, S., additional, Zimmerman, T., additional, Gay, C., additional, Huth, J., additional, Oliver, J., additional, Iwata, Y., additional, Ohmoto, T., additional, Ohsugi, T., additional, Barnett, B., additional, Cammerata, J., additional, Skarha, J., additional, Bruner, N., additional, Frautschi, M., additional, Gold, M., additional, Hoeferkamp, M., additional, Kingsberry, P., additional, Matthews, J., additional, Yu, L., additional, Seidel, S., additional, Thomas, T.L., additional, Wells, S., additional, Tamura, N., additional, Bacchetta, N., additional, Bisello, D., additional, Castro, A., additional, Paccagnella, A., additional, Boudreau, J., additional, Engels, E., additional, Hu, P., additional, Huffman, T., additional, Shepard, P., additional, Vandenbrink, S., additional, Bedeschi, F., additional, Belforte, S., additional, Bonaccorso, C., additional, Franceschi, A., additional, Galeotti, S., additional, Giannetti, P., additional, Menzione, A., additional, Morsani, F., additional, Dell'Orso, M., additional, Punzi, G., additional, Raffaelli, F., additional, Ristori, L., additional, Zetti, F., additional, Bortoletto, D., additional, Garfinkel, A., additional, Hardmann, A., additional, Hoffman, K., additional, Shaw, N.M., additional, Done, J., additional, Kamon, T., additional, Scarpine, V., additional, Trost, H.-J., additional, Wolinski, J., additional, Benjamin, D., additional, Sill, A., additional, Hou, J-F., additional, Ely, R., additional, Haber, C., additional, Kipnis, I., additional, Kleinfelder, S., additional, and Milgrome, O., additional
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- 1995
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36. Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?
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Lindenmeyer, M., Spörri, S., Stäubli, M., Studer, A., and Studer, H.
- Abstract
1The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3′ triiodothyronine (T3) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T4→ T3conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea‐pigs.2Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5′,3′ triiodothyronine (reverse T3), indicating effective inhibition of T4→ T3conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine).3While amiodarone induced bradycardia, iopanoic acid did not change the heart rate.4Supraphysiological amounts of exogenous T3reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline.5The intracellular inhibition of the T4→ T3conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T3at its receptor or somewhere later along the pathway from the T3‐receptor interaction to the final effect of T3on heart rate. The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3′ triiodothyronine (T3) was investigated. For this purpose we compared the effect of amiodarone with that of another potent inhibitor of the T4→ T3conversion, i.e. the radiographic contrast medium iopanoic acid, on the heart rate of unanaesthetized guinea‐pigs. Both amiodarone and, to an even greater extent, iopanoic acid induced an increase in serum 3.5′,3′ triiodothyronine (reverse T3), indicating effective inhibition of T4→ T3conversion. Both amiodarone and iopanoic acid were accumulated in the liver and in the heart (measured as iodine). While amiodarone induced bradycardia, iopanoic acid did not change the heart rate. Supraphysiological amounts of exogenous T3reverted the amiodarone induced bradycardia to near normal values. A comparable effect was observed with isoprenaline. The intracellular inhibition of the T4→ T3conversion is not the ultimate mode of the action of the amiodarone effect on heart rate. It is thought that amiodarone interacts with T3at its receptor or somewhere later along the pathway from the T3‐receptor interaction to the final effect of T3on heart rate.
- Published
- 1984
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37. The CDF-II detector: Technical design report
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Blair, R., Byrum, Karen L., Dawson, J., Guarino, V., Kuhlmann, S., Lecompte, Thomas Joseph, Nodulman, L., Proudfoot, James, Wagner, Robert G., Wicklund, Arthur Barry, Breccia, L., Deninno, M., Fiori, I., Mazzanti, Paolo, Piacentino, G. M., Rimondi, F., Semeria, F., Zucchelli, S., Behrends, S., Bensinger, James R., Blocker, Craig Alan, Kirsch, Lawrence E., Lamoureux, J., Bonushkin, Y., Chase, F., Dworkin, L., Hauser, J., Lindgren, Michael Allen, Saltzberg, David Paul, Scott, A., Shi, Y., Amadon, Alexis, Berryhill, Jeffrey W., Contreras, M., Culbertson, Ray L., Dusatko, J., Frisch, Henry J., Grosso-Pilcher, C., Hohlmann, Marcus, Northrup, R., Sanders, H., Shochet, Melvyn J., Toback, David A., Wahl, J., Wilson, P., Fortney, L., Goshaw, Alfred T., Kowald, W., Lee, Alfred Mcclung, Oh, S. H., Phillips, Thomas J., Robertson, W. H., Wang, C., Albrow, Michael G., Anderson, J., Andresen, J., Atac, M., Barsotti, E., Beretvas, Andrew F., Berge, J. P., Biery, K., Binkley, Morris, Bossert, R., Bowden, M., Buckley-Geer, E., Byon-Wagner, A., Carter, H., Chappa, S., Cihangir, Selcuk, Cooper, G., Dejongh, Don Frederic, Demaat, R., Demina, R., Derwent, P., Drake, G., Elias, John E., Erdmann, W., Flaugher, B., Foster, G. William, Freeman, J., Gao, M., Geer, S., Goeransson, G., Grozis, C., Hahn, Stephen R., Harris, Robert M., Haynes, B., Herber, Randolph J., Holm, S., Howell, J., Hrycyk, M., Husby, D., Incandela, Joseph R., Jensen, H., Joshi, Umeshwar P., Kephart, Robert D., Kerby, J., Knopf, Walter R., Kroll, J., Lammel, S., Lewis, Jonathan D., Limon, P., Lindenmeyer, M., Lukens, P., Maeshima, Kaori, Miao, Ting, Mukherjee, A., Nelson, C., Newman-Holmes, Catherine, Nobrega, F., Pangburn, J., Patrick, J., Pavlicek, V., Petravick, D., Pitts, K., Plunkett, R., Pordes, Ruth, Ratzmann, P., Rivetta, C., Schlabach, P., Schmidt, Eugene E., Segler, S., Sexton-Kennedy, Elizabeth, Shaw, T., Shenai, A., Silva, R., Spalding, J., Spiegel, Leonard Gordon, Srage, J., Stanek, R., Streets, Jonathan Mark, Stuart, D., Tkaczyk, S., Tollestrup, Alvin V., Tang, Z., Treptow, K., Vidal, R., Wagner, R. L., Wands, R., Wester, William Carl, Wicklund, Eric J., Woodbury, K., Yagil, A., Yeh, Gong Ping, Yoh, J., Yarema, R., Yu, I., Zimmermann, S., Zimmerman, T., Zmuda, T., Konigsberg, Jacobo, Klimenko, Sergey, Korytov, A., Mitselmakher, Guenakh, Nomerotski, Andrei, Barone, M., Cordelli, M., Donno, F., Parri, A., Sansoni, A., Clark, Allan Geoffrey, Couyoumtzelis, C., Kambara, H., Speer, Thomas, Wu, X., Franklin, M., Gay, C., Huth, John Edward, Spiropulu, Maria, Troconiz, J. F., Handa, Takanobu, Iwata, Y., Kurino, K., Nakano, I., Ohmoto, T., Ohsugi, T., Takashima, Ryuichi, Christofek, Leonard Steven, Costello, J., Downing, R., Errede, D., Errede, Steven Michael, Fan, Qun, Holloway, L., Keup, R., Liss, Tony M., Roser, Robert M., Simaitis, V., Strologas, John, Cropp, R., Hinrichsen, B., Kellerbauer, A., Kim, H., Kordas, K., Ragan, Kenneth J., Robinson, A., Saab, T., Sinervo, Pekka K., Strahl, K., Taylor, W., Theoret, C., Trischuk, William, Warburton, Andreas T., Barnett, Bruce A., Blumenfeld, Barry J., Feng, Z., Gerdes, David W., Guimaraes, J., Orndorff, J., Smith, C., Snider, F., Abe, F., Fukui, Yasuo, Kohriki, T., Morita, Y., Nagasaka, Yasushi, Mikamo, S., Unno, Y., Ashmanskas, William Joseph, Carithers, William C., Einsweiler, K., Ely, Robert P., Galtieri, L., Garcia-Sciveres, Maurice, Haber, Carl H., Kim, Young-Kee, Lancaster, M., Lys, J., Milgrome, Oren, Paulini, M., Reher, D., Shapiro, M., Shuman, D., Siegrist, J., Wenzel, Hans J., Yao, W., Bauer, G., Friedman, J., Hafen, Elizabeth Scott, Kelley, K., Ngan, C. Y. P., Rosenson, Lawrence, Shah, T., Sphicas, Paraskevas, Sumorok, K., Tether, S., Tseng, J., Vucinic, D., Bromberg, Carl Michael, Huston, J., Miller, R., Murgia, Simona, Richards, R., Wolinski, J., Amidei, Dante E., Campbell, M., Chapman, J., Huang, Z., James, Eric B., Kelly, M., Mann, J., Murphy, C., Tecchio, M., Truitt, S., Vejcik, S., Winn, D., Wolinski, David S., Bailey, Mark W., Bruner, N., Gold, Michael S., Hoeferkamp, M., Matthews, J., Moore, E., Seidel, Sally Carol, Tannenbaum, Benn, Thomas, T. L., Worm, Steven D., Yu, L., Hoftiezer, J., Hughes, R., Koehn, Phillip Todd, Winer, B., Kato, Y., Nakamura, K., Okusawa, T., Toyoda, Haruki, Yoshida, T., Azzi, P., Bacchetta, Nicola, Bisello, Dario, Busetto, Giovanni, Castro, Andrea, Dorigo, T., Gotra, Yuri N., Loreti, Maurizio, Mariotti, M., Pescara, L., Praticelli, N., Ribon, A., Stanco, Luca, Wyss, J., Bevensee, B., Gallinaro, Michele, Heinrich, Joel, Holck, C., Robert Plunkett, Kononenko, Walter, Lockyer, Nigel S., Long, Owen R., Metzler, S., Newcomer, F. Mitchell, Oliveira, R., Ukegawa, Fumihiko, Berg, Richard, Williams, H. H., Amendolia, R., Basti, A., Bedeschi, Franco, Belforte, Stefano, Bettelli, S., Bellettini, Giorgio, Cervelli, F., Chiarelli, Giorgio, Cocca, E., Orso, Mauro, Donati, S., Ferretti, C., Gatti, P., Galeotti, S., Giannetti, P., Giusti, G., Incagli, M., Lami, Stefano, Lanzoni, M., Leone, Sandra, Lucchesi, D., Mangano, Michelangelo L., Menzione, A., Meschi, Emilio, Morsani, F., Murat, P., Paoletti, R., Parashar, N., Pasuello, D., Punzi, G., Raffaelli, F., Rapisarda, S., Ristori, L., Scribano, A., Spinella, F., Stefanini, A., Turini, N., Velev, G., Wallace, N. B., Zetti, F., Boudreau, J., Engels, E., Huffman, Brian T., Rosati, R., Shepard, P., Barnes, V., Bolla, G., Bortoletto, D., Garfinkel, A. F., Hardman, A., Hoffman, Kara Dion, Keaffaber, T., Laasanen, Alvin Toivo, Shaw, N. M., Barbaro, Pawel, Blusk, Steven Roy, Bodek, Arie, Budd, Howard Scott, Cassada, J., Chan, K. M., Kim, Bock-Joo, Kruse, Mark Charles, Liu, J., Sakumoto, W., Tipton, Paul Louis, Tollefson, K., Ye, H., Akopian, A., Apollinari, G., Bagdasarov, S., Bhatti, Anwar Ahmad, Demortier, Luc, Giokaris, N., Goulianos, Konstantin A., Khazins, D., Melese, P., Mesropian, Christina, Titov, A., Conway, John S., Devlin, Thomas J., Jacobs, V., Loomis, C., Valls, Juan A., Walsh, M., Watts, T., Antos, J., Chang, P. S., Chang, P. T., Cheng, M. T., Chu, M. L., Guo, R. S., Liu, Y. C., Teng, P. K., Wang, C. H., Wang, Ming-Jer, Wu, S. C., Yeh, P., Chertok, Maxwell Benjamin, Done, J., Kamon, Teruki, Mcintyre, Peter M., Webb, Robert C., Benjamin, Douglas P., Frautschi, Mark A., Ganel, O., Hao, W., Liu, Q., Papadimitriou, Vaia, Sill, A., Wigmans, Richard, Aota, S., Asakawa, T., Hara, Kazuhiko, Ikeda, H., Kikuchi, T., Kim, S., Kondo, K., Kuwabara, T., Minato, H., Miyashita, S., Nakada, H., Seiya, Yoshihiro, Shibayama, T., Suzuki, J., Suzuki, T., Takano, T., Takikawa, Koji, Tanaka, M., Uchida, T., Watanabe, T., Yasuoka, K., Karr, K., Sliwa, K., Timko, M., Akimoto, H., Arisawa, T., Fujimoto, Y., Hasegawa, S., Iwai, J., Terashi, Koji, Uesaka, S., Yoda, Y., Bellinger, James Nugent, Carlsmith, Duncan L., Chung, W., Handler, R., Ott, G., Lusin, S., Pondrom, Lee, Chandler, T., Feild, R. G., Kasha, Henry, Martin, A., Pappas, S., Schmidt, M., Wandersee, A., Budagov, Yu, Cambiaghi, M., Caner, A., Cauz, D., Chlachidze, G., Cobal-Grassmann, Marina, Gerard, G., Grassmann, H., Hartmann, F., Introzzi, G., Kesten, P., Knoblauch, D., Kongeter, A., Kovacs, E., Mishina, M., Moggi, N., Muller, T., Musy, M., Neuberger, D., Pagliarone, C., Pauletta, G., Penzo, A., Perazzo, A., Rodrigo, T., Rolli, Simona, Santi, L., Semenov, A., Strohmer, R., Tartarelli, Giuseppe Francesco, Chirikov, I., Tung, M., Vilar, Rocio, and Zanetti, Anna Maria
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Detectors and Experimental Techniques
38. Loss of endogenous thymosin β4 accelerates glomerular disease
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Vasilopoulou, E, Kolatsi-Joannou, M, Lindenmeyer, M, White, K, Robson, M, Cohen, C, Sebire, N, Riley, P, Winyard, P, and Long, D
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podocyte ,Nephrology ,inflammation ,urogenital system ,fibrosis ,cytoskeleton ,glomerulus ,urologic and male genital diseases ,hormones, hormone substitutes, and hormone antagonists - Abstract
Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin \(\beta_4\) regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin \(\beta_4\) improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin \(\beta_4\) in the kidney is unknown. We demonstrate that thymosin β4 is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin \(\beta_4\) did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin \(\beta_4\) in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin \(\beta_4\) in the migration of these cells. Thymosin \(\beta_4\) knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin \(\beta_4\) is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression.
39. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice
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Godel, M., Hartleben, B., Herbach, N., Liu, S., Zschiedrich, S., Lu, S., Debreczeni-Mor, A., Lindenmeyer, M. T., Rastaldi, M. -P., Hartleben, G., Wiech, T., Fornoni, A., Nelson, R. G., Kretzler, M., Wanke, R., Pavenstadt, H., Kerjaschki, D., Cohen, C. D., Hall, M. N., Ruegg, M. A., Inoki, K., Walz, G., and Huber, T. B.
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3. Good health
40. Compartment specific expression of dendritic cell markers in human glomerulonephritis.
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Segerer, S., Heller, F., Lindenmeyer, M. T., Schmid, H., Cohen, C. D., Draganovici, D., Mandelbaum, J., Nelson, P. J., Gröne, H.-J., Gröne, E. F., Figel, A.-M., Nössner, E., and Schlöndorff, D.
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- *
MACROPHAGES , *DENDRITIC cells , *ANTIGEN presenting cells , *LYMPHOID tissue , *BONE marrow , *IMMUNOHISTOCHEMISTRY , *HISTOCHEMISTRY - Abstract
Macrophages and dendritic cells are heterogenous and highly plastic bone marrow-derived cells that play major roles in renal diseases. We characterized these cells using immunohistochemistry in 55 renal biopsies from control patients or patients with glomerulonephritis as an initial step towards postulating specific roles for these cells in kidney disease. In proliferative glomerulonephritis numerous CD68 positive (pan monocyte, macrophage and dendritic marker) cells were found in both glomeruli and the tubulointerstitial space, however, a myeloid dendritic cell marker (DC-SIGN) was identified only in the tubulointerstitium. A significant number of plasmacytoid dendritic cells (identified as BDCA-2 positive cells) were seen at sites of interstitial inflammation, including follicular aggregates of inflammatory cells. Langerin positive cells (a marker of Langerhans' cells) were detectable but rare. The area of either CD68 or DC-SIGN positive interstitial cells correlated with serum creatinine. Low levels of DC-SIGN, DC-LAMP and MHC class II mRNA were present in the tubulointerstitial space in controls and increased only in that region in proliferative glomerulonephritis. We demonstrate that the CD68 positive cells infiltrating the glomerulus lack dendritic cell markers (reflecting macrophages), whereas in the tubulointerstitial space the majority of CD68 positive cells are also DC-SIGN positive (reflecting myeloid dendritic cells). Their number correlated with serum creatinine, which further emphasizes the significance of interstitial DCs in progressive glomerular diseases.Kidney International (2008) 74, 37–46; doi:10.1038/ki.2008.99; published online 26 March 2008 [ABSTRACT FROM AUTHOR]
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- 2008
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41. Dendritic cells in experimental renal inflammation - Part I
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Maja T. Lindenmeyer, Elfriede Noessner, Peter J. Nelson, Stephan Segerer, University of Zurich, and Lindenmeyer, M
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10017 Institute of Anatomy ,Physiology ,Disease stages ,610 Medicine & health ,chemical and pharmacologic phenomena ,Biology ,Kidney ,Mice ,03 medical and health sciences ,0302 clinical medicine ,1311 Genetics ,Genetics ,medicine ,Animals ,Humans ,10035 Clinic for Nephrology ,030304 developmental biology ,0303 health sciences ,Nephritis ,Innate immune system ,2727 Nephrology ,Follicular dendritic cells ,Glomerulonephritis ,Dendritic Cells ,General Medicine ,Renal inflammation ,1314 Physiology ,Acquired immune system ,medicine.disease ,Phenotype ,Dendritic cells ,Interstitial inflammation ,Experimental renal inflammation ,Disease Models, Animal ,Nephrology ,Immunology ,Mouse Kidney ,570 Life sciences ,biology ,030215 immunology - Abstract
Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. While descriptions of cells with dendritic morphology in rodent kidneys date back to the early 1970s, a network of DCs in the mouse kidney has only recently been described. DCs acquire distinct phenotypic and functional characteristics depending on the microenvironment and the disease stages. Concomitantly, their communication with cells of the adaptive immunity might have tissue-protective or tissue-deleterious consequences. This review summarizes results from recent studies on the role of DCs in experimental renal inflammation.
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- 2011
42. Optimized protocol for the multi-omics processing of cryopreserved human kidney tissue.
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Gies SE, Hänzelmann S, Kylies D, Lassé M, Lagies S, Hausmann F, Khatri R, Zolotarev N, Poets M, Zhang T, Demir F, Billing AM, Quaas J, Meister E, Engesser J, Mühlig AK, Lu S, Liu S, Chilla S, Edenhofer I, Czogalla J, Braun F, Kammerer B, Puelles VG, Bonn S, Rinschen MM, Lindenmeyer M, and Huber TB
- Abstract
Biobanking of tissue from clinically obtained kidney biopsies for later use with multi-omic and imaging techniques is an inevitable step to overcome the need of disease model systems and towards translational medicine. Hence, collection protocols ensuring integration into daily clinical routines using preservation media not requiring liquid nitrogen but instantly preserving kidney tissue for clinical and scientific analyses are of paramount importance. Thus, we modified a robust single nucleus dissociation protocol for kidney tissue stored snap frozen or in the preservation media RNA later and CellCover. Using porcine kidney tissue as surrogate for human kidney tissue, we conducted single nucleus RNA sequencing with the Chromium 10X Genomics platform. The resulting data sets from each storage condition were analyzed to identify any potential variations in transcriptomic profiles. Furthermore, we assessed the suitability of the preservation media for additional analysis techniques (proteomics, metabolomics) and the preservation of tissue architecture for histopathological examination including immunofluorescence staining. In this study, we show that in daily clinical routines the RNA later facilitates the collection of highly preserved human kidney biopsies and enables further analysis with cutting-edge techniques like single nucleus RNA sequencing, proteomics, and histopathological evaluation. Only metabolome analysis is currently restricted to snap frozen tissue. This work will contribute to build tissue biobanks with well-defined cohorts of the respective kidney disease that can be deeply molecularly characterized, opening new horizons for the identification of unique cells, pathways and biomarkers for the prevention, early identification, and targeted therapy of kidney diseases.
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- 2024
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43. Zyxin is important for the stability and function of podocytes, especially during mechanical stretch.
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Kliewe F, Siegerist F, Hammer E, Al-Hasani J, Amling TRJ, Hollemann JZE, Schindler M, Drenic V, Simm S, Amann K, Daniel C, Lindenmeyer M, Hecker M, Völker U, and Endlich N
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- Humans, Mice, Animals, Zyxin genetics, Zyxin metabolism, Actin Cytoskeleton metabolism, Kidney Glomerulus, Focal Adhesions metabolism, Podocytes metabolism, Hypertension, Renal, Nephritis
- Abstract
Podocyte detachment due to mechanical stress is a common issue in hypertension-induced kidney disease. This study highlights the role of zyxin for podocyte stability and function. We have found that zyxin is significantly up-regulated in podocytes after mechanical stretch and relocalizes from focal adhesions to actin filaments. In zyxin knockout podocytes, we found that the loss of zyxin reduced the expression of vinculin and VASP as well as the expression of matrix proteins, such as fibronectin. This suggests that zyxin is a central player in the translation of mechanical forces in podocytes. In vivo, zyxin is highly up-regulated in patients suffering from diabetic nephropathy and in hypertensive DOCA-salt treated mice. Furthermore, zyxin loss in mice resulted in proteinuria and effacement of podocyte foot processes that was measured by super resolution microscopy. This highlights the essential role of zyxin for podocyte maintenance in vitro and in vivo, especially under mechanical stretch., (© 2024. The Author(s).)
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- 2024
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44. GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation.
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von Rauchhaupt E, Klaus M, Ribeiro A, Honarpisheh M, Li C, Liu M, Köhler P, Adamowicz K, Schmaderer C, Lindenmeyer M, Steiger S, Anders HJ, and Lech M
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- Humans, Mice, Animals, Puromycin Aminonucleoside adverse effects, Puromycin Aminonucleoside metabolism, Growth Differentiation Factor 15 genetics, Growth Differentiation Factor 15 metabolism, Creatinine metabolism, Inflammation metabolism, Mice, Knockout, Podocytes metabolism, Kidney Diseases metabolism
- Abstract
GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a Gdf15 -deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of Xbp1 and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. Gdf15 knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin-creatinine ratio (ACR), were increased in Gdf15 knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in Gdf15 -deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.
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- 2024
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45. Evolution of hypoxia and hypoxia-inducible factor asparaginyl hydroxylase regulation in chronic kidney disease.
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Faivre A, Dissard R, Kuo W, Verissimo T, Legouis D, Arnoux G, Heckenmeyer C, Fernandez M, Tihy M, Rajaram RD, Delitsikou V, Le NA, Spingler B, Mueller B, Shulz G, Lindenmeyer M, Cohen C, Rutkowski JM, Moll S, Scholz CC, Kurtcuoglu V, and de Seigneux S
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- Humans, Animals, Mice, X-Ray Microtomography, Repressor Proteins genetics, Down-Regulation, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Mixed Function Oxygenases genetics, Mixed Function Oxygenases metabolism, Hypoxia
- Abstract
Background: The roles of hypoxia and hypoxia inducible factor (HIF) during chronic kidney disease (CKD) are much debated. Interventional studies with HIF-α activation in rodents have yielded contradictory results. The HIF pathway is regulated by prolyl and asparaginyl hydroxylases. While prolyl hydroxylase inhibition is a well-known method to stabilize HIF-α, little is known about the effect asparaginyl hydroxylase factor inhibiting HIF (FIH)., Methods: We used a model of progressive proteinuric CKD and a model of obstructive nephropathy with unilateral fibrosis. In these models we assessed hypoxia with pimonidazole and vascularization with three-dimensional micro-computed tomography imaging. We analysed a database of 217 CKD biopsies from stage 1 to 5 and we randomly collected 15 CKD biopsies of various severity degrees to assess FIH expression. Finally, we modulated FIH activity in vitro and in vivo using a pharmacologic approach to assess its relevance in CKD., Results: In our model of proteinuric CKD, we show that early CKD stages are not characterized by hypoxia or HIF activation. At late CKD stages, some areas of hypoxia are observed, but these are not colocalizing with fibrosis. In mice and in humans, we observed a downregulation of the HIF pathway, together with an increased FIH expression in CKD, according to its severity. Modulating FIH in vitro affects cellular metabolism, as described previously. In vivo, pharmacologic FIH inhibition increases the glomerular filtration rate of control and CKD animals and is associated with decreased development of fibrosis., Conclusions: The causative role of hypoxia and HIF activation in CKD progression is questioned. A pharmacological approach of FIH downregulation seems promising in proteinuric kidney disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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46. Kidney outcome after mild to moderate COVID-19.
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Schmidt-Lauber C, Hänzelmann S, Schunk S, Petersen EL, Alabdo A, Lindenmeyer M, Hausmann F, Kuta P, Renné T, Twerenbold R, Zeller T, Blankenberg S, Fliser D, and Huber TB
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- Humans, SARS-CoV-2, Albuminuria, Cohort Studies, Prospective Studies, Pandemics, Hematuria, Cross-Sectional Studies, Kidney, Disease Progression, COVID-19 complications, COVID-19 epidemiology, Pyuria
- Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a remarkable kidney tropism. While kidney effects are common in severe coronavirus disease 2019 (COVID-19), data on non-severe courses are limited. Here we provide a multilevel analysis of kidney outcomes after non-severe COVID-19 to test for eventual kidney sequela., Methods: This cross-sectional study investigates individuals after COVID-19 and matched controls recruited from the Hamburg City Health Study (HCHS) and its COVID-19 program. The HCHS is a prospective population-based cohort study within the city of Hamburg, Germany. During the COVID-19 pandemic the study additionally recruited subjects after polymerase chain reaction-confirmed SARS-CoV-2 infections. Matching was performed by age, sex and education. Main outcomes were estimated glomerular filtration rate (eGFR), albuminuria, Dickkopf3, haematuria and pyuria., Results: A total of 443 subjects in a median of 9 months after non-severe COVID-19 were compared with 1328 non-COVID-19 subjects. The mean eGFR was mildly lower in post-COVID-19 than non-COVID-19 subjects, even after adjusting for known risk factors {β = -1.84 [95% confidence interval (CI) -3.16 to -0.52]}. However, chronic kidney disease [odds ratio (OR) 0.90 (95% CI 0.48-1.66)] or severely increased albuminuria [OR 0.76 (95% CI 0.49-1.09)] equally occurred in post-COVID-19 and non-COVID-19 subjects. Haematuria, pyuria and proteinuria were also similar between the two cohorts, suggesting no ongoing kidney injury after non-severe COVID-19. Further, Dickkopf3 was not increased in the post-COVID-19 cohort, indicating no systematic risk for ongoing GFR decline [β = -72.19 (95% CI -130.0 to -14.4)]., Conclusion: While mean eGFR was slightly lower in subjects after non-severe COVID-19, there was no evidence for ongoing or progressive kidney sequela., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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47. The ShGlom Assay Combines High-Throughput Drug Screening With Downstream Analyses and Reveals the Protective Role of Vitamin D3 and Calcipotriol on Podocytes.
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Ristov MC, Lange T, Artelt N, Nath N, Kuss AW, Gehrig J, Lindenmeyer M, Cohen CD, Gul S, Endlich K, Völker U, and Endlich N
- Abstract
Chronic kidney disease (CKD) is a major public health burden affecting more than 500 million people worldwide. Podocytopathies are the main cause for the majority of CKD cases due to pathogenic morphological as well as molecular biological alterations of postmitotic podocytes. Podocyte de-differentiation is associated with foot process effacement subsequently leading to proteinuria. Since currently no curative drugs are available, high throughput screening methods using a small number of animals are a promising and essential tool to identify potential drugs against CKD in the near future. Our study presents the implementation of the already established mouse Glom Assay as a semi-automated high-throughput screening method-shGlom Assay -allowing the analysis of several hundreds of FDA-verified compounds in combination with downstream pathway analysis like transcriptomic and proteomic analyses from the same samples, using a small number of animals. In an initial prescreening we have identified vitamin D3 and its analog calcipotriol to be protective on podocytes. Furthermore, by using RT-qPCR, Western blot, and RNA sequencing, we found that mRNA and protein expression of nephrin, the vitamin D receptor and specific podocyte markers were significantly up-regulated due to vitamin D3- and calcipotriol-treatment. In contrast, kidney injury markers were significantly down-regulated. Additionally, we found that vitamin D3 and calcipotriol have had neither influence on the expression of the miR-21 and miR-30a nor on miR-125a/b, a miRNA described to regulate the vitamin D receptor. In summary, we advanced the established mouse Glom Assay to a semi-automated high-throughput assay and combined it with downstream analysis techniques by using only a minimum number of animals. Hereby, we identified the vitamin D signaling pathway as podocyte protective and to be counteracting their de-differentiation., Competing Interests: JG is an employee of the DITABIS AG, Pforzheim, Germany and the ACQUIFER Imaging GmbH, Heidelberg, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ristov, Lange, Artelt, Nath, Kuss, Gehrig, Lindenmeyer, Cohen, Gul, Endlich, Völker and Endlich.)
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- 2022
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48. Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease.
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Verissimo T, Faivre A, Rinaldi A, Lindenmeyer M, Delitsikou V, Veyrat-Durebex C, Heckenmeyer C, Fernandez M, Berchtold L, Dalga D, Cohen C, Naesens M, Ricksten SE, Martin PY, Pugin J, Merlier F, Haupt K, Rutkowski JM, Moll S, Cippà PE, Legouis D, and de Seigneux S
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- Animals, Humans, Kidney metabolism, Kidney Tubules, Proximal metabolism, Mice, Retrospective Studies, Gluconeogenesis physiology, Renal Insufficiency, Chronic metabolism
- Abstract
Introduction: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown., Methods: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit., Results: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies., Conclusion: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis., (Copyright © 2022 by the American Society of Nephrology.)
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- 2022
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49. α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier.
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Rogg M, Maier JI, Van Wymersch C, Helmstädter M, Sammarco A, Lindenmeyer M, Zareba P, Montanez E, Walz G, Werner M, Endlich N, Benzing T, Huber TB, and Schell C
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- Animals, Integrins metabolism, Mice, Mice, Knockout, Glomerular Filtration Barrier metabolism, Microfilament Proteins metabolism, Podocytes metabolism
- Abstract
Background: The cell-matrix adhesion between podocytes and the glomerular basement membrane is essential for the integrity of the kidney's filtration barrier. Despite increasing knowledge about the complexity of integrin adhesion complexes, an understanding of the regulation of these protein complexes in glomerular disease remains elusive., Methods: We mapped the in vivo composition of the podocyte integrin adhesome. In addition, we analyzed conditional knockout mice targeting a gene ( Parva ) that encodes an actin-binding protein (α-parvin), and murine disease models. To evaluate podocytes in vivo , we used super-resolution microscopy, electron microscopy, multiplex immunofluorescence microscopy, and RNA sequencing. We performed functional analysis of CRISPR/Cas9-generated PARVA single knockout podocytes and PARVA and P ARVB double knockout podocytes in three- and two-dimensional cultures using specific extracellular matrix ligands and micropatterns., Results: We found that PARVA is essential to prevent podocyte foot process effacement, detachment from the glomerular basement membrane, and the development of FSGS. Through the use of in vitro and in vivo models, we identified an inherent PARVB -dependent compensatory module at podocyte integrin adhesion complexes, sustaining efficient mechanical linkage at the filtration barrier. Sequential genetic deletion of PARVA and PARVB induces a switch in structure and composition of integrin adhesion complexes. This redistribution of these complexes translates into a loss of the ventral actin cytoskeleton, decreased adhesion capacity, impaired mechanical resistance, and dysfunctional extracellular matrix assembly., Conclusions: The findings reveal adaptive mechanisms of podocyte integrin adhesion complexes, providing a conceptual framework for therapeutic strategies to prevent podocyte detachment in glomerular disease., (Copyright © 2022 by the American Society of Nephrology.)
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- 2022
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50. GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus.
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Lorenz G, Ribeiro A, von Rauchhaupt E, Würf V, Schmaderer C, Cohen CD, Vohra T, Anders HJ, Lindenmeyer M, and Lech M
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- Humans, Mice, Animals, Mice, Inbred C57BL, Disease Models, Animal, Ligands, Growth Differentiation Factor 15, Lupus Erythematosus, Systemic, Interferon Type I, Autoimmune Diseases
- Abstract
Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15-/- C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system., (© 2022 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2022
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