| Mechanical forces and TGFbeta1 reduce podocyte adhesion through alpha3beta1 integrin downregulation. | |
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MedLine Citation:
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PMID: 19420102 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Podocyturia is a marker of diabetic nephr- opathy, a possible determinant of its progression and a powerful risk factor for cardiovascular disease. A reduction in podocyte adhesion to the glomerular basement membrane (GBM) via downregulation of alpha3beta1 integrin expression, the main podocyte anchoring dimer to the GBM, may represent one of the mechanisms of podocyturia in glomerular disease. This study investigated the role of mechanical forces and transforming growth factor beta1 (TGFbeta1) in podocyte adhesion and integrin expression. METHODS: Conditionally immortalized murine podocytes were exposed to mechanical stretch and/or TGFbeta1 for 48 h. Podocyte adhesion, apoptosis and alpha3beta1 integrin expression were assessed. RESULTS: Stretch and TGFbeta1 significantly reduced podocyte adhesion and alpha3beta1 integrin expression, events paralleled by increased apoptosis. Blockade of beta1 integrin, with a specific antibody, demonstrated a reduced podocyte adhesion indicating that beta1 integrin downregulation was required for the loss of podocyte adhesion. This was linked to an increase in podocyte apoptosis. The role of apoptosis in podocyte adhesion was further investigated using caspase-3 inhibitors. Podocyte apoptosis inhibition did not affect stretch- and TGFbeta1-mediated integrin downregulation and the loss of podocyte adhesion, suggesting that alpha3beta1 integrin downregulation is sufficient to alter cell adhesion. Although stretch significantly increased podocyte TGFbeta type I, II and III receptors but not podocyte TGFbeta1 secretion, the combination of stretch and TGFbeta1 did not show any additive or synergistic effects on podocyte adhesion and alpha3beta1 integrin expression. CONCLUSIONS: These results suggest that downregulation of alpha3beta1 integrin expression, by mechanical forces or TGFbeta1, is per se sufficient to reduce podocyte adhesion. Apoptosis may represent a parallel important determinant of the podocyte loss from the GBM. |
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Authors:
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Cecile Dessapt; Marc Olivier Baradez; Anthea Hayward; Alessandra Dei Cas; Stephen M Thomas; Giancarlo Viberti; Luigi Gnudi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-06 |
Journal Detail:
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Title: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Volume: 24 ISSN: 1460-2385 ISO Abbreviation: Nephrol. Dial. Transplant. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-18 Completed Date: 2009-12-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706402 Medline TA: Nephrol Dial Transplant Country: England |
Other Details:
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Languages: eng Pagination: 2645-55 Citation Subset: IM |
Affiliation:
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King's College London, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology Cell Adhesion / drug effects, physiology Cells, Cultured Down-Regulation / drug effects Extracellular Matrix / physiology Glomerular Basement Membrane / cytology, drug effects, physiology Glycosylation Integrin alpha3beta1 / chemistry, physiology* Kidney Diseases / etiology, pathology, physiopathology Mice Podocytes / cytology, drug effects*, physiology* Receptors, Transforming Growth Factor beta / classification, physiology Stress, Mechanical Transforming Growth Factor beta1 / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Integrin alpha3beta1; 0/Receptors, Transforming Growth Factor beta; 0/Transforming Growth Factor beta1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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