9 results on '"Katharina Groll"'
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2. Publisher Correction: Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning
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Matthias Weider, Laura Julia Starost, Katharina Groll, Melanie Küspert, Elisabeth Sock, Miriam Wedel, Franziska Fröb, Christian Schmitt, Tina Baroti, Anna C. Hartwig, Simone Hillgärtner, Sandra Piefke, Tanja Fadler, Marc Ehrlich, Corinna Ehlert, Martin Stehling, Stefanie Albrecht, Ammar Jabali, Hans R. Schöler, Jürgen Winkler, Tanja Kuhlmann, and Michael Wegner
- Subjects
Science - Abstract
The originally published version of this Article omitted Tanja Kuhlmann and Michael Wegner as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.
- Published
- 2018
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3. Influx of T cells into corpus callosum increases axonal injury, but does not change the course of remyelination in toxic demyelination
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Elif Nur Yilmaz, Stefanie Albrecht, Katharina Groll, Christian Thomas, Lutz Wallhorn, Martin Herold, Stephanie Hucke, Luisa Klotz, and Tanja Kuhlmann
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Cellular and Molecular Neuroscience ,Neurology - Abstract
Multiple sclerosis (MS) is a focal inflammatory and demyelinating disease. The inflammatory infiltrates consist of macrophages/microglia, T and B cells. Remyelination (RM) is an endogenous repair process which frequently fails in MS patients. In earlier studies, T cells either promoted or impaired RM. Here, we used the combined cuprizone/MOG-EAE model to further dissect the functional role of T cells for RM. The combination of MOG immunization with cuprizone feeding targeted T cells to the corpus callosum and increased the extent of axonal injury. Global gene expression analyses demonstrated significant changes in the inflammatory environment; however, additional MOG immunization did not alter the course of RM. Our results suggest that the inflammatory environment in the combined model affects axons and oligodendrocytes differently and that oligodendroglial lineage cells might be less susceptible to T cell mediated injury.
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- 2022
4. Atheroprotective effects of 17β-oestradiol are mediated by peroxisome proliferator-activated receptor γ in human coronary artery smooth muscle cells
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Vedat Tiyerili, Ulrich M. Becher, Katharina Groll, J Jehle, Georg Nickenig, and Sandra Adler
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Neointimal hyperplasia ,Agonist ,chemistry.chemical_classification ,medicine.drug_class ,17β-oestradiol ,propylpyrazole triol ,Antagonist ,Peroxisome proliferator-activated receptor ,General Medicine ,Pharmacology ,medicine.disease ,chemistry.chemical_compound ,Basic Research ,human coronary artery smooth muscle cells ,chemistry ,In vivo ,medicine ,peroxisome-proliferator-activated-receptor-γ ,LY294002 ,oestrogen receptor α ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
Introduction17β-oestradiol (E2) mediates vasculoprotection in various preclinical and clinical models of atherosclerosis and neointimal hyperplasia. However, the molecular mechanisms underlying these effects are still not fully elucidated. Previous studies have demonstrated the essential role of the peroxisome-proliferator-activated-receptor-γ (PPARγ) in mediating vasculoprotective effects of E2 in vivo. The aim of the current study was to investigate whether PPARγ mediates vasculoprotective mechanisms of E2 in human coronary artery smooth muscle cells (HCASMC).Material and methodsPrimary HCASMC were stimulated with E2 (10 nM), the selective oestrogen receptor α (ERα) agonist propylpyrazole triol (PPT) (50 nM) and the selective ERα antagonist methyl-piperidino-pyrazole (MPP) (1 µM), respectively. Changes in PPARγ mRNA, protein expression, and DNA binding affinity were assessed.ResultsE2 significantly increased PPARγ expression in HCASMC (1.95 ±0.41-fold; n = 5; p = 0.0335). This effect was mimicked by ERα agonist PPT (1.63 ±0.27-fold; n = 7; p = 0.0489) and was abrogated by co-incubation with ERα antagonist MPP (1.17 ±0.18-fold; n = 3; pvs. control > 0.05). PPARγ-DNA binding activity to PPRE remained unchanged upon stimulation with E2 (0.94 ±0.11-fold; n = 4; pvs. control > 0.05). Pharmacological inhibition of PI3K/Akt by LY294002 abrogated E2-induced expression of PPARγ (0.24 ±0.09-fold; n = 3; pvs. E2 = 0.0017).ConclusionsThe present study identifies PPARγ as an important downstream mediator of E2-related atheroprotective effects in HCASMC. PPARγ agonism might be a promising therapeutic strategy to prevent neointimal hyperplasia and consecutive cardiovascular events in postmenopausal women with depleted E2 plasma levels.
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- 2020
5. G protein-coupled estrogen receptor GPR30 exerts vasoprotective effects in apolipoprotein E-deficient mice
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Sandra Adler, Moritz Nöthel, Ulrich M. Becher, Georg Nickenig, J Jehle, Vedat Tiyerili, and Katharina Groll
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chemistry.chemical_classification ,Apolipoprotein E ,medicine.medical_specialty ,Reactive oxygen species ,business.industry ,General Medicine ,Vasoprotective ,Endocrinology ,chemistry ,Internal medicine ,medicine ,Deficient mouse ,business ,GPER - Abstract
IntroductionGPR30 is an intracellular transmembrane G protein-coupled receptor that mediates non-genomic estrogen signaling. The GPR30 agonist G-1 modulates glucose homeostasis and vascular function. However, its impact on vascular inflammation and atherogenesis has not yet been investigated in the atherosclerotic apolipoprotein E-deficient(ApoE-/-) mouse model.Material and methodsApoE-/- mice were fed a high-cholesterol diet for 7 weeks while being treated with the selective GPR30 agonist G-1 (n=6-7). After the treatment period, vascular relaxation capacity, vascular oxidative stress, and atherosclerotic plaque burden were assessed. In vitro, reactive oxygen species, expression levels of the angiotensin II type1(AT1) receptor, and proliferation rate were quantified in human coronary artery smooth muscle cells(HCASMC).ResultsG-1 significantly improved glucose tolerance in vivo (142.2±8.1mg/dl vs. 204.6±13.3mg/dl), G-1 reduced vascular oxidative stress (221±88RLU/s/mg vs.1,983±885RLU/s/mg) and improved endothelium-dependent vasodilation (relaxation to 35.1±4.5% vs.63.0±4.6%). Furthermore, treatment with G-1 significantly reduced the atherosclerotic plaque burden of female ApoE-/- mice (56.5±3.7% vs.75.5±2.9%). In vitro, G-1 provoked a significant downregulation of the AT1 receptor in HCASMC (0.67±0.09-fold). Furthermore, G-1 blunted angiotensin II-induced ROS production by HCASMC (817±7RLU/s/mg vs.1,625±105 RLU/s/mg) and diminished HCASMC proliferation (-26.8±2.7% vs.+50.4±1.7%).ConclusionsSelective GPR30 activation improves glucose tolerance in vivo and decreases vascular ROS production in vitro and in vivo. In vitro, the antioxidant effect might be mediated by downregulation of the AT1 receptor. In vivo, the antioxidant effect of G-1 is associated with an improved endothelial function and a reduced atherosclerotic plaque burden in ApoE-deficient mice, indicating beneficial vascular effects of GPR30 activation. GPR30 agonism might thus be a compelling treatment strategy against atherosclerosis.
- Published
- 2021
6. P720Atheroprotective effects of 17beta-estradiol are mediated by PPARgamma in human coronary artery smooth muscle cells
- Author
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Sandra Adler, Katharina Groll, Tiyerili, Ulrich M. Becher, J Jehle, and Georg Nickenig
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Neointimal hyperplasia ,medicine.medical_specialty ,Phosphoinositide 3-kinase ,biology ,business.industry ,Akt/PKB signaling pathway ,Estrogen receptor ,17beta estradiol ,medicine.disease ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,biology.protein ,Signal transduction ,Cardiology and Cardiovascular Medicine ,business ,Bromodeoxyuridine ,Artery - Abstract
Background 17β-estradiol (E2) mediates vasculoprotection in various preclinical and clinical models of atherosclerosis and neointimal hyperplasia. However, the molecular mechanisms underlying these effects are still not fully elucidated. Previous studies have demonstrated the essential role of the peroxisome-proliferator-activated-receptor-γ (PPARγ) in mediating vasculoprotective effects of E2 in vivo. The aim of the current study was to investigate whether PPARγ is implicated in mediating vasculoprotective mechanisms of E2 in human coronary artery smooth muscle cells (HCASMC). Methods Primary HCASMC were purchased and stimulated with E2 [10 nM], the selective estrogen receptor α (ERα) agonist propylpyrazole triol (PPT) [50 nM] and the selective ERα antagonist methyl-piperidino-pyrazole (MPP) [1 μM], respectively. Changes in PPARγ mRNA and protein expression upon stimulation of ERα were assessed by qPCR and Western blot analyses. Nuclear PPARγ protein expression and DNA binding affinity was assessed after the isolation of the nuclear protein fraction. Hereafter, HCASMC were incubated with E2, PPARγ-antagonist GW9662 [1 μM – 30 μM], or both. HCASMC proliferation was assessed by nuclear BrdU staining and reactive oxygen species (ROS) formation was assessed by L-012- and DCF-DA assays. Results E2 significantly increased PPARγ expression in HCASMC (1.95±0.41 –fold; n=5; p=0.0335). This effect was mimicked by ERα agonist PPT (1.63±0.27 –fold; n=7; p=0.0489) and was abrogated by co-incubation with ERα antagonist MPP (1.17±0.18 –fold; n=3; pvs. control >0.05). Nuclear PPARγ expression was enhanced by E2 (1.53±0.16 –fold; n=4; pvs. control = 0.0074; Fig. 2A) whereas PPARγ's DNA binding activity to PPRE remained unchanged upon stimulation with E2 (0.94±0.11 –fold; n=4; pvs. control >0.05). Pharmacological inhibition of PI3K/Akt by LY294002 abrogated E2-induced expression of PPARγ (0.24±0.09 –fold; n=3; pvs. E2 = 0.0017), arguing for a PI3K/Akt-dependent activation by E2. The role of PPARγ in mediating vasculoprotective effects of E2 was assessed in functional assays using PPARγ-antagonist GW9662. E2 diminished HCASMC proliferation which was restored by GW9662. While E2 only slightly decreased ROS production by HCASMC, GW9662 significantly increased ROS levels (1,036±169 RLU x s–1 x cell–1 versus 561±99 RLU x s–1 x cell–1; n=5–6; p=0.0287). Conclusion In summary, the present study identifies PPARγ as a downstream mediator of E2-related atheroprotective effects in HCASMC. 17β-estradiol regulates vascular PPARγ-expression in HCASMC via the ERα receptor and the PI3K/Akt pathway. PPARγ agonism might be a promising therapeutic strategy to prevent cardiovascular events in postmenopausal women with depleted E2 plasma levels. Acknowledgement/Funding This work was supported by the Bonfor program of the University of Bonn [grant number O-109.0057 to JJ].
- Published
- 2019
7. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion
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Sven Moyzio, Markus Horsthemke, Michael Sixt, Sandra A. Hemkemeyer, Martin Bähler, Roland Wedlich-Söldner, Peter J. Hanley, Sebastian Tacke, Anne C. Bachg, Barbara Müther, and Katharina Groll
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0301 basic medicine ,Phagocytic cup ,Genotype ,Phagocytosis ,Green Fluorescent Proteins ,Immunology ,Motility ,Saccharomyces cerevisiae ,macromolecular substances ,CDC42 ,Myosins ,Biology ,Biochemistry ,law.invention ,Mice ,03 medical and health sciences ,Confocal microscopy ,law ,CDC2 Protein Kinase ,Animals ,Macrophage ,Pseudopodia ,cdc42 GTP-Binding Protein ,Molecular Biology ,Actin ,Mice, Knockout ,Microscopy, Confocal ,Chemotaxis ,Cell Biology ,Hydrogen-Ion Concentration ,Cell biology ,Toll-Like Receptor 4 ,Phenotype ,030104 developmental biology ,Mutation ,Macrophages, Peritoneal ,Filopodia ,Gene Deletion - Abstract
Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.
- Published
- 2017
8. Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning
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Jürgen Winkler, Simone Hillgärtner, Michael Wegner, Marc Ehrlich, Stefanie Albrecht, Tanja Kuhlmann, Sandra Piefke, Christian Schmitt, Miriam Wedel, Corinna Ehlert, Franziska Fröb, Elisabeth Sock, Martin Stehling, Ammar Jabali, Melanie Küspert, Matthias Weider, Hans R. Schöler, Anna C. Hartwig, Tina Baroti, Katharina Groll, Laura Starost, and Tanja Fadler
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0301 basic medicine ,Science ,Cellular differentiation ,Oligodendrocyte Transcription Factor 2 ,General Physics and Astronomy ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,OLIG2 ,Evolution, Molecular ,03 medical and health sciences ,Myelin ,Mice ,medicine ,Animals ,Humans ,lcsh:Science ,Transcription factor ,Conserved Sequence ,Myelin Sheath ,Homeodomain Proteins ,Multidisciplinary ,NFATC Transcription Factors ,SOXE Transcription Factors ,Calcineurin ,Oligodendrocyte differentiation ,Nuclear Proteins ,NFAT ,Cell Differentiation ,General Chemistry ,Zebrafish Proteins ,Publisher Correction ,Cell biology ,Rats ,Oligodendroglia ,030104 developmental biology ,medicine.anatomical_structure ,Homeobox Protein Nkx-2.2 ,Gene Expression Regulation ,lcsh:Q ,Signal Transduction ,Transcription Factors - Abstract
Oligodendrocytes produce myelin for rapid transmission and saltatory conduction of action potentials in the vertebrate central nervous system. Activation of the myelination program requires several transcription factors including Sox10, Olig2, and Nkx2.2. Functional interactions among them are poorly understood and important components of the regulatory network are still unknown. Here, we identify Nfat proteins as Sox10 targets and regulators of oligodendroglial differentiation in rodents and humans. Overall levels and nuclear fraction increase during differentiation. Inhibition of Nfat activity impedes oligodendrocyte differentiation in vitro and in vivo. On a molecular level, Nfat proteins cooperate with Sox10 to relieve reciprocal repression of Olig2 and Nkx2.2 as precondition for oligodendroglial differentiation and myelination. As Nfat activity depends on calcium-dependent activation of calcineurin signaling, regulatory network and oligodendroglial differentiation become sensitive to calcium signals. NFAT proteins are also detected in human oligodendrocytes, downregulated in active multiple sclerosis lesions and thus likely relevant in demyelinating disease., Oligodendrocyte differentiation is known to depend on transcription factors Sox10, Nkx2.2, and Olig2. Here, the authors show that Nfat/calcineurin signaling contributes to oligodendrocyte differentiation by relieving mutual repression of Nkx2.2 and Olig2.
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- 2017
9. Publisher Correction: Nfat/calcineurin signaling promotes oligodendrocyte differentiation and myelination by transcription factor network tuning
- Author
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Tanja Kuhlmann, Anna C. Hartwig, Christian Schmitt, Miriam Wedel, Franziska Fröb, Ammar Jabali, Melanie Küspert, Tina Baroti, Laura Starost, Jürgen Winkler, Simone Hillgärtner, Michael Wegner, Stefanie Albrecht, Marc Ehrlich, Matthias Weider, Corinna Ehlert, Hans R. Schöler, Tanja Fadler, Elisabeth Sock, Martin Stehling, Sandra Piefke, and Katharina Groll
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Multidisciplinary ,Calcineurin signaling ,Science ,Oligodendrocyte differentiation ,General Physics and Astronomy ,NFAT ,General Chemistry ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,lcsh:Q ,lcsh:Science ,Neuroscience ,Transcription factor ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,030217 neurology & neurosurgery - Abstract
The originally published version of this Article omitted Tanja Kuhlmann and Michael Wegner as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.
- Published
- 2018
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