15 results on '"Rastaldi MP"'
Search Results
2. Atypical IgM on T cells predict relapse and steroid dependence in idiopathic nephrotic syndrome.
- Author
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Colucci M, Carsetti R, Rosado MM, Cascioli S, Bruschi M, Candiano G, Corpetti G, Giardino L, Serafinelli J, Giannone C, Ghiggeri GM, Rastaldi MP, Sitia R, Emma F, and Vivarelli M
- Subjects
- Adolescent, Child, Child, Preschool, Drug Resistance genetics, Drug Therapy, Combination methods, Female, Follow-Up Studies, Glucocorticoids therapeutic use, Humans, Immunoglobulin M analysis, Immunoglobulin M immunology, Infant, Male, Nephrotic Syndrome blood, Nephrotic Syndrome genetics, Nephrotic Syndrome immunology, Podocytes, Prospective Studies, Recurrence, Rituximab pharmacology, Rituximab therapeutic use, Sialic Acids metabolism, T-Lymphocytes metabolism, Treatment Outcome, Glucocorticoids pharmacology, Immunoglobulin M metabolism, Nephrotic Syndrome drug therapy, T-Lymphocytes immunology
- Abstract
The clinical heterogeneity of idiopathic nephrotic syndrome in childhood may reflect different mechanisms of disease that are as yet unclear. Here, we evaluated the association between an atypical presence of IgM on the surface of T cells (T-cell IgM) and the response to steroid therapy in a total of 153 pediatric patients with idiopathic nephrotic syndrome in different phases of disease. At disease onset, T-cell IgM median levels were significantly elevated and predictive of risk of relapse in 47 patients. They were also significantly increased comparing 58 steroid-dependent to 8 infrequently relapsing and 14 frequently relapsing patients, especially during relapse, whereas they were within the normal range in 7 genetic steroid-resistant patients. T-cell IgM in vivo was not affected by the amount of total circulating IgM, nor by concomitant acute infections or oral immunosuppression. However, it was affected by rituximab treatment in 21 steroid-dependent patients. By in vitro experiments, elevated T-cell IgM was not influenced by total circulating IgM levels or by the presence of other circulating factors, and there was no distinctive antigen-specificity or atypical IgM polymerization. Rather, we found that increased T-cell IgM correlates with reduced IgM sialylation, which influences T-cell response to steroid inhibition and T-cell production of podocyte-damaging factors. Thus, the atypical presence of IgM on the surface of T cells may predispose a subset of steroid-sensitive pediatric patients with idiopathic nephrotic syndrome to a poor response to steroid therapy since disease onset., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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3. Cystinosin deficiency causes podocyte damage and loss associated with increased cell motility.
- Author
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Ivanova EA, Arcolino FO, Elmonem MA, Rastaldi MP, Giardino L, Cornelissen EM, van den Heuvel LP, and Levtchenko EN
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- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Adolescent, Amino Acid Transport Systems, Neutral deficiency, Amino Acid Transport Systems, Neutral genetics, Case-Control Studies, Cell Adhesion, Cell Line, Child, Child, Preschool, Cystinosis genetics, Cystinosis pathology, Cystinosis urine, Cytoskeletal Proteins genetics, Cytoskeletal Proteins metabolism, Cytoskeleton metabolism, Down-Regulation, Female, Genetic Predisposition to Disease, Humans, Male, Mutation, Phenotype, Phosphorylation, Podocytes drug effects, Podocytes pathology, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt metabolism, Sialoglycoproteins genetics, Sialoglycoproteins metabolism, Signal Transduction, Urine cytology, WT1 Proteins genetics, WT1 Proteins metabolism, Young Adult, Amino Acid Transport Systems, Neutral metabolism, Cell Movement drug effects, Cystinosis metabolism, Podocytes metabolism
- Abstract
The involvement of the glomerulus in the pathogenesis of cystinosis, caused by loss-of-function mutations in cystinosin (CTNS, 17p13), is a matter of controversy. Although patients with cystinosis demonstrate glomerular lesions and high-molecular-weight proteinuria starting from an early age, a mouse model of cystinosis develops only signs of proximal tubular dysfunction. Here we studied podocyte damage in patients with cystinosis by analyzing urinary podocyte excretion and by in vitro studies of podocytes deficient in cystinosin. Urine from patients with cystinosis presented a significantly higher amount of podocytes compared with controls. In culture, cystinotic podocytes accumulated cystine compatible with cystinosin deficiency. The expression of podocyte specific genes CD2AP, podocalyxin, and synaptopodin and of the WT1 protein was evident in all cell lines. Conditionally immortalized podocyte lines of 2 patients with different CTNS mutations had altered cytoskeleton, impaired cell adhesion sites, and increased individual cell motility. Moreover, these cells showed enhanced phosphorylation of both Akt1 and Akt2 (isoforms of protein kinase B). Inhibition of Akt by a specific inhibitor (Akti inhibitor 1/2) resulted in normalization of the hypermotile phenotype. Thus, our study extends the list of genetic disorders causing podocyte damage and provides the evidence of altered cell signaling cascades resulting in impaired cell adhesion and enhanced cell motility in cystinosis., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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4. Deficiency of cannabinoid receptor of type 2 worsens renal functional and structural abnormalities in streptozotocin-induced diabetic mice.
- Author
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Barutta F, Grimaldi S, Franco I, Bellini S, Gambino R, Pinach S, Corbelli A, Bruno G, Rastaldi MP, Aveta T, Hirsch E, Di Marzo V, and Gruden G
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- Acetylglucosamine urine, Albuminuria etiology, Albuminuria metabolism, Animals, Bone Marrow Transplantation, Cell Line, Cell Proliferation, Chemokine CCL2 metabolism, Chemotaxis, Leukocyte, Creatinine blood, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Experimental physiopathology, Diabetic Nephropathies genetics, Diabetic Nephropathies metabolism, Diabetic Nephropathies pathology, Diabetic Nephropathies physiopathology, Extracellular Matrix metabolism, Female, Kidney Glomerulus pathology, Kidney Glomerulus physiopathology, Mice, Inbred C57BL, Mice, Knockout, Monocytes metabolism, Podocytes metabolism, Receptor, Cannabinoid, CB2 genetics, Receptors, CCR2 metabolism, Time Factors, Diabetes Mellitus, Experimental complications, Diabetic Nephropathies etiology, Kidney Glomerulus metabolism, Receptor, Cannabinoid, CB2 deficiency, Streptozocin
- Abstract
A functionally active endocannabinoid system is present within the kidney. The cannabinoid receptor type 2 (CB2) is expressed by both inflammatory cells and podocytes, and its activation has beneficial effects in experimental diabetic nephropathy. To further explore the role of CB2 in diabetic nephropathy, we studied renal functional and structural abnormalities in streptozotocin-induced diabetic CB2 knockout mice. In diabetic mice, deletion of the CB2 receptor albuminuria, the downregulation of podocin and nephrin, mesangial expansion, overexpression of extracellular matrix components, monocyte infiltration, and reduced renal function were all exacerbated. To investigate the relative contributions of podocytes and monocytes to the phenotype of diabetic knockout mice, bone marrow transplantation experiments were performed. The lack of CB2 on bone marrow-derived cells was shown to be important in driving the enhanced glomerular monocyte accrual found in diabetic knockout mice. Absence of CB2 on resident glomerular cells had a major role in worsening diabetic nephropathy, both functional and structural abnormalities, likely by enhanced MCP-1 and CB1 signaling. Studies in cultured podocytes demonstrated that CB2 expression is not altered by a high glucose milieu but is downregulated by mechanical stretch, mimicking glomerular capillary hypertension. Thus, CB2 deletion worsens diabetic nephropathy, independent of bone marrow-derived cells.
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- 2014
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5. The authors reply:.
- Author
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Haas M, Rastaldi MP, and Fervenza F
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- Humans, Glomerulonephritis, IGA pathology, Kidney Glomerulus pathology, Lupus Nephritis pathology
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- 2014
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6. Histologic classification of glomerular diseases: clinicopathologic correlations, limitations exposed by validation studies, and suggestions for modification.
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Haas M, Rastaldi MP, and Fervenza FC
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- 2014
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7. Calcium sensing in podocytes.
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Rastaldi MP
- Subjects
- Animals, Cytoskeleton metabolism, Glomerulosclerosis, Focal Segmental drug therapy, Podocytes cytology, Receptors, Calcium-Sensing metabolism
- Abstract
Besides its primary function in maintaining systemic calcium homeostasis, the calcium-sensing receptor (CaSR) is expressed by many cell types, with different, sometimes opposite, regulatory functions. Novel work from Oh and collaborators shows that activation of CaSR in podocytes has prosurvival effects and protects the cell from puromycin aminonucleoside damage. Given that the cellular consequences of CaSR activation are largely context-dependent, further studies will be required to elucidate its precise role in podocyte physiology and pathophysiology.
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- 2011
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8. Apoptosis in the kidneys of patients with type II diabetic nephropathy.
- Author
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Verzola D, Gandolfo MT, Ferrario F, Rastaldi MP, Villaggio B, Gianiorio F, Giannoni M, Rimoldi L, Lauria F, Miji M, Deferrari G, and Garibotto G
- Subjects
- Biopsy, Case-Control Studies, Cholesterol, LDL blood, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies physiopathology, Fas Ligand Protein metabolism, Glomerular Filtration Rate, Glycated Hemoglobin analysis, Humans, Immunohistochemistry, Kidney surgery, Kidney Glomerulus metabolism, Kidney Tubules blood supply, Multivariate Analysis, Up-Regulation, fas Receptor metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Apoptosis physiology, Diabetes Mellitus, Type 2 pathology, Diabetic Nephropathies pathology, Kidney pathology
- Abstract
The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.
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- 2007
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9. Functional consequences of integrin-linked kinase activation in podocyte damage.
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Teixeira Vde P, Blattner SM, Li M, Anders HJ, Cohen CD, Edenhofer I, Calvaresi N, Merkle M, Rastaldi MP, and Kretzler M
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- Active Transport, Cell Nucleus, Animals, Cytoskeletal Proteins metabolism, DNA-Binding Proteins metabolism, Enzyme Activation, Lymphoid Enhancer-Binding Factor 1, Male, Mice, Mice, Inbred BALB C, Trans-Activators metabolism, Transcription Factors metabolism, beta Catenin, Kidney Glomerulus pathology, Protein Serine-Threonine Kinases physiology
- Abstract
Background: The delicate foot process architecture of glomerular podocytes critically depends on integrin mediated cell-glomerular basement membrane (GBM) interaction. Integrin signaling via the integrin-linked kinase (ILK) is activated in podocyte damage and associated with considerable podocyte phenotype alterations. ILK has been shown to regulate cell fate via nuclear interaction of beta-catenin with lymphoid enhancer factor (LEF-1) transcription factors. The aim of this study was to elucidate the molecular mechanisms of ILK dependant phenotype regulation in podocytes., Methods: ILK function was evaluated in conditionally immortalized murine glomerular epithelial cells using overexpression of ILK and a small molecule ILK inhibitor in puromycin/adriamycin-induced podocyte damage in vitro and in vivo., Results: Kinase active, but not mutant ILK induced translocation of beta-catenin to the cell nucleus, de novo expression of LEF-1, and nuclear colocalization of beta-catenin and LEF-1. The role of ILK signaling in podocyte damage was evaluated using puromycin, an agent known to cause selective proteinuria and to increase ILK activity. The small molecular ILK inhibitor MC-5 blocked puromycin-induced nuclear translocation of beta-catenin, podocyte detachment, cell proliferation, and repression of the slit membrane molecules P-cadherin and CD2ap. In vivo activation of the beta-catenin pathway could be shown by nuclear colocalization of beta-catenin with WT-1 in adriamycin nephropathy., Conclusion: ILK regulates podocyte cell matrix interaction, proliferation, and slit membrane gene expression in podocyte damage. As this pathway is amendable to pharmacologic intervention, further detailed studies of in vivo ILK function in glomerular disease appear justified.
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- 2005
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10. Human renal epithelial cells produce the long pentraxin PTX3.
- Author
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Nauta AJ, de Haij S, Bottazzi B, Mantovani A, Borrias MC, Aten J, Rastaldi MP, Daha MR, van Kooten C, and Roos A
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- C-Reactive Protein genetics, CD40 Ligand pharmacology, Cells, Cultured, Complement C1q metabolism, Epithelial Cells metabolism, Humans, Interleukin-1 pharmacology, RNA, Messenger analysis, Serum Amyloid P-Component genetics, Tumor Necrosis Factor-alpha pharmacology, C-Reactive Protein biosynthesis, Kidney metabolism, Serum Amyloid P-Component biosynthesis
- Abstract
Background: Pentraxin 3 (PTX3) is a prototypic long pentraxin with structural similarities in the C-terminal domain to the classical short pentraxins C-reactive protein (CRP) and serum amyloid P component. PTX3 is suggested to play an important role in the innate resistance against pathogens, regulation of inflammatory reactions, and clearance of apoptotic cells. Unlike the classic pentraxins, PTX3 is mainly expressed extrahepatically. The present study was designed to investigate the expression of PTX3 by human proximal renal tubular epithelial cells (PTECs)., Methods: PTECs were cultured in the presence or absence of inflammatory cytokines. PTX3 mRNA expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) in human kidney and PTECs. PTX3 protein levels in PTEC cultures were quantified by enzyme-linked immunosorbent assay (ELISA)., Results: PTX3 mRNA was shown to be constitutively expressed in human kidney. Constitutive expression and production of PTX3 was shown in primary mesangial cells, in primary PTECs, and in renal fibroblasts. Further analysis showed that interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) stimulation strongly enhanced the expression and production of PTX3 in PTECs in a dose- and time-dependent manner. In addition, activation of PTECs with IL-17 and CD40L, respectively, but not with IL-6 or IL-4, resulted in strongly increased production of PTX3, whereas granulocyte macrophage-colony-stimulating factor (GM-CSF) inhibited IL-1-induced PTX3 production. PTX3 produced by PTEC is functionally active in binding C1q., Conclusion: These results indicate that PTX3 is expressed and released by PTECs and that in proinflammatory conditions PTX3 production is up-regulated. Local expression of PTX3 may play a role in the innate immune response and inflammatory reactions in the kidney.
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- 2005
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11. Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis.
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Bruschi M, Catarsi P, Candiano G, Rastaldi MP, Musante L, Scolari F, Artero M, Carraro M, Carrea A, Caridi G, Zennaro C, Sanna-Cherchi S, Viola FB, Ferrario F, Perfumo F, and Ghiggeri GM
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- Adolescent, Adult, Apolipoproteins E blood, Apolipoproteins E genetics, Apolipoproteins E urine, Child, Child, Preschool, Cohort Studies, Female, Genotype, Glomerulosclerosis, Focal Segmental blood, Glomerulosclerosis, Focal Segmental genetics, Glomerulosclerosis, Focal Segmental urine, Humans, Kidney metabolism, Male, Nephrotic Syndrome blood, Nephrotic Syndrome genetics, Nephrotic Syndrome urine, Apolipoproteins E metabolism, Glomerulosclerosis, Focal Segmental metabolism, Nephrotic Syndrome metabolism
- Abstract
Background: Hyperlipemia characterizes nephrotic syndrome (NS) and contributes to the progression of the underlying nephropathy. The data in the literature support an implication of apolipoprotein E (apoE) in both hyperlipemia and focal segmental glomerulosclerosis (FSGS), a malignant condition associated with NS., Methods: The apoE genotype was determined in 209 nephrotic patients, who were classified according to age and their response to steroids as resistant children (N = 96) and adults (43), and steroid dependent (33) and steroid responder (37) children. A total of 123 presented the histological features of FSGS. In a subgroup of 28 patients, serum and urinary levels of apoE and renal deposits were evaluated by immunofluorescence., Results: The allelic frequencies of the three major haplotypes epsilon2, epsilon3, and epsilon4 were the same in nephrotic patients versus controls, and homozygosity for epsilon3epsilon3 was comparably the most frequent genotype (70 vs. 71%) followed by epsilon3epsilon4, epsilon2epsilon3, epsilon2epsilon4, epsilon4epsilon4. Serum levels of apoE were fivefold higher in NS and in FSGS patients than in controls, with a direct correlation with hypercholesterolemia and proteinuria. ApoE genotypes did not influence serum levels. Urinary levels were 1/10,000 of serum with an increment in nephrotic urines. Finally, immunofluorescence demonstrated the absence of apoE in sclerotic glomeruli, while comparably nephrotic patients with membranous nephropathy had an increased glomerular expression of apoE., Conclusions: ApoE is dysregulated in NS with a marked increment in serum, which is a part of the complex lipid metabolism. Down-regulation of glomerular apoE instead is a peculiarity of FSGS and may contribute to the pathogenesis of the disease. The normal distribution of apoE genotypes in nephrotic patients with FSGS excludes a pathogenetic role of genetic variants.
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- 2003
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12. Depletion of clusterin in renal diseases causing nephrotic syndrome.
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Ghiggeri GM, Bruschi M, Candiano G, Rastaldi MP, Scolari F, Passerini P, Musante L, Pertica N, Caridi G, Ferrario F, Perfumo F, and Ponticelli C
- Subjects
- Adolescent, Adult, Aged, Clusterin, Cohort Studies, Female, Fluorescent Antibody Technique, Glomerulonephritis, Membranous blood, Glomerulonephritis, Membranous complications, Glomerulonephritis, Membranous urine, Glomerulosclerosis, Focal Segmental blood, Glomerulosclerosis, Focal Segmental complications, Glomerulosclerosis, Focal Segmental urine, Glycoproteins urine, Humans, Kidney Glomerulus metabolism, Male, Middle Aged, Molecular Chaperones urine, Nephrotic Syndrome urine, Glycoproteins blood, Molecular Chaperones blood, Nephrotic Syndrome blood, Nephrotic Syndrome etiology
- Abstract
Background: Clusterin is a lipoprotein that has anti-complement effects in membranous nephropathy (MN). In focal segmental glomerulosclerosis (FSGS), it inhibits permeability plasma factor activity and could influence proteinuria. Moreover, with aging, knockout mice for clusterin develop a progressive glomerulopathy with sclerosis., Methods: Since little is known about clusterin metabolism in humans, we determined clusterin levels and composition in the sera and urine of 23 patients with MN, 25 with FSGS and 23 with steroid-responsive nephrotic syndrome (NS). Renal localization was evaluated by immunofluorescence and morphometry., Results: Serum clusterin was markedly reduced in active MN, in FSGS and in children with NS compared to controls; after stable remission of proteinuria, nearly normal levels were restored. Among various biochemical variables, serum clusterin was inversely correlated with hypercholesterolemia. Urinary clusterin, representing a 0.01 fraction of serum, was higher in the urine from normal subjects and FSGS patients in remission with proteinuric MN, FSGS and idiopathic NS; clusterin was inversely correlated with proteinuria. In all cases, urinary and serum clusterin was composed of the same 80 kD isoforms. Finally, a decrease in focal segmental or global clusterin staining was found in FSGS glomeruli, especially in areas of sclerosis. Instead, in MN an overall increment of staining was observed that ranged from mild/focal to very intense/diffuse., Conclusions: The overall pool of clusterin is reduced in glomerular diseases causing nephrotic syndrome, with hypercholesterolemia appearing as the unifying feature. Depletion of clusterin should negatively affect the clinical outcome in nephrotic patients and efforts should be aimed at normalizing clusterin overall pool.
- Published
- 2002
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13. Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies.
- Author
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Rastaldi MP, Ferrario F, Giardino L, Dell'Antonio G, Grillo C, Grillo P, Strutz F, Müller GA, Colasanti G, and D'Amico G
- Subjects
- Actins analysis, Biopsy, Cell Differentiation, Cell Division, Collagen biosynthesis, Epithelial Cells pathology, Humans, Immunohistochemistry, Kidney Tubules metabolism, Phenotype, Procollagen-Proline Dioxygenase analysis, Proliferating Cell Nuclear Antigen analysis, Vimentin biosynthesis, Extracellular Matrix metabolism, Kidney Diseases pathology, Kidney Tubules pathology
- Abstract
Background: In recent studies performed on cultured cells and experimental nephropathies, it has been hypothesized that tubular epithelial cells (TEC), via epithelial-mesenchymal transformation (EMT), can become collagen-producing cells. According to this theory, they should proceed through several activating steps, such as proliferation and phenotype changes, to eventually synthesize extracellular matrix (ECM)., Methods: To evaluate whether EMT operates in human TECs, 133 renal biopsies of different renal diseases were studied, analyzing by immunohistochemistry and in situ hybridization the possible expression of markers of proliferation (PCNA, Mib-1), cellular phenotype (vimentin, alpha-SMA, cytokeratin, ZO-1) and ECM production (prolyl 4-hydroxylase, HSP47, interstitial collagens)., Results: Independently of histological diagnosis, variable degrees of TEC positivity for PCNA (2.7 +/- 2.4 cells/field) and Mib-1 (1.9 +/- 2.3) were present. TECs expressing vimentin (1.4 +/- 4.7) and alpha-smooth muscle actin (alpha-SMA; 0.04 +/- 0.4) also were detected. It was possible to observe loss of epithelial antigens from 8 to 10% of the tubular cross sections. Moreover, TECs were stained by prolyl 4-hydroxylase (3.6 +/- 4.3), heat shock protein-47 (HSP47; 2.9 +/- 5.4), collagen type I (0.2 +/- 2.7) and type III (0.3 +/- 2.0). Collagen types I and III mRNAs were found in 0.8 to 1.4 cells/field. The number of TEC with EMT features were associated with serum creatinine and the degree of interstitial damage (P< or = 0.03), and even considering the 45 cases with mild interstitial lesions, the tubular expression of all markers remained strictly associated with renal function (P< or = 0.01)., Conclusions: Our results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes. Moreover, the association of EMT features with serum creatinine supports the value of these markers in the assessment of disease severity.
- Published
- 2002
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14. Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases.
- Author
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Wang SX, Rastaldi MP, Pätäri A, Ahola H, Heikkilä E, and Holthöfer H
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- Amino Acid Sequence, Antibodies, Monoclonal, Biopsy, Epitopes immunology, Gene Expression, Humans, Immunoenzyme Techniques, Kidney Diseases pathology, Kidney Glomerulus pathology, Kidney Glomerulus physiopathology, Membrane Proteins, Molecular Sequence Data, Proteins immunology, Proteinuria pathology, Kidney Diseases physiopathology, Proteins genetics, Proteinuria physiopathology
- Abstract
Background: Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier., Methods: Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria-associated protein expression was developed in various diagnostic groups of human kidney biopsies., Results: In normal control kidney, antibodies to intracellular and extracellular nephrin domain showed a typical podocyte pattern of reactivity, while the 18C7 antibody to a normally inaccessible proteinuria-associated epitope was negative. Instead, strong glomerular positivity by 18C7 was seen in membranous glomerulonephropathy, membranoproliferative glomerulonephritis, systemic lupus erythematosus and cryoglobulinemic nephritis, while with antibodies to either intracellular or extracellular nephrin domains, a down-regulation in nephrin expression pattern was shown., Conclusions: Unmasking or de novo expression of distinct glomerular proteins may be an important feature reflecting the pathophysiological events in these diseases with altered glomerular permeability, while only mild changes in the slit diaphragm protein nephrin appear to take place.
- Published
- 2002
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15. Idiopathic IgA nephropathy with segmental necrotizing lesions of the capillary wall.
- Author
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D'Amico G, Napodano P, Ferrario F, Rastaldi MP, and Arrigo G
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- Adult, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Biopsy, Capillaries pathology, Cyclophosphamide therapeutic use, Disease Progression, Drug Therapy, Combination, Female, Glomerulonephritis, IGA drug therapy, Glomerulonephritis, IGA metabolism, Glomerulonephritis, IGA physiopathology, Glucocorticoids therapeutic use, Humans, Immunohistochemistry, Immunosuppressive Agents therapeutic use, Male, Methylprednisolone therapeutic use, Necrosis, Prednisone therapeutic use, Survival Analysis, Glomerulonephritis, IGA pathology, Renal Circulation
- Abstract
Background: Segmental glomerular necrosis has been described in the biopsy material in a minority of patients with idiopathic IgA nephropathy in the oldest studies on this disease, but this marker of active capillaritis has received little attention in the subsequent literature, and its significance and relevance for the clinical outcome is still unknown., Methods: Thirty-five out of 340 patients (10.3%) biopsied in our division at the San Carlo Hospital since 1974 showed active segmental necrotizing lesions. The morphological features and the natural history of this group of patients were compared with those of a control group of 229 patients who had comparable serum creatinine and extent of glomerular sclerosis, but who lacked active segmental necrosis., Results: Patients with the necrotic variant showed a significantly more marked extracapillary proliferation and interstitial accumulation of monocytes and T lymphocytes and, in the segmental areas of necrotizing and extracapillary lesions, infiltration of monocytes, deposition of fibrinogen, and expression of the adhesion molecule vascular cell adhesion molecule-1. No difference was found in the presenting clinical syndrome. The clinical course was frequently characterized by acute flare ups, and the progression to end-stage renal failure was more frequent, although actuarial renal survival was not significantly worse (P = 0.07). The aggressive treatment with steroids and cyclophosphamide, carried out in 20 of the 35 patients, has probably been beneficial, justifying the multicenter controlled trial that recently has been initiated., Conclusions: Vasculitic lesions of the glomerular capillaries, with histologic and immunohistological features similar to those of Henoch-Schönlein purpura and antineutrophil cytoplasmic antibody-positive renal vasculitis, were found in 10% of patients with idiopathic IgAN. Clinical features at presentation did not differ from those of the other patients with IgAN, and despite of the more frequent occurrences of recurrent acute flare ups, rapid progression to end-stage renal failure was a rare phenomenon, even in untreated patients.
- Published
- 2001
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