NDT Advance Access published online on April 19, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh837
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1 Renal-Electrolyte and Hypertension Division of the University of Pennsylvania, Philadelphia, PA, USA
* To whom correspondence should be addressed. Background. The podocyte is bathed in an angiotensin II (AngII)-rich ultrafiltrate, but the impact of AngII on podocyte pathobiology is not well known. Because podocytes play a direct role in the glomerular basement membrane (GBM) thickening of diabetes, the Methods. Cultured mouse podocytes were treated with various doses of AngII for selected periods of time, with or without inhibitors of TGF- Results. AngII Conclusions. AngII stimulates the podocyte to produce
Received October 18, 2004
Accepted March 21, 2005
Original Articles
Angiotensin II stimulates
3(IV) collagen production in mouse podocytes via TGF-
and VEGF signalling: implications for diabetic glomerulopathy
2 Cellular Biology Unit, Department of Biology, Universidad Autónoma de Madrid, Spain
3 Division of Nephrology/Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
4 Klinik für Innere Medizin III, University of Jena, Jena, Germany
Sheldon Chen, E-mail: chens{at}mail.med.upenn.edu
Abstract 
3(IV) collagen chain was examined. Podocyte expression of 3(IV) collagen may involve the transforming growth factor-
(TGF-) and vascular endothelial growth factor (VEGF) systems. and VEGF signalling, SB-431542 and SU5416, respectively. TGF-1 and VEGF were assayed by enzyme-linked immunosorbent assay (ELISA); 3(IV) collagen, TGF- type II receptor and phospho-Smad2 were assayed by immunoblotting.
10-10 M was found to stimulate the production of 3(IV) collagen significantly in as short a time as 3 h. The expression of 3(IV) collagen was influenced by the TGF- system, but AngII did not increase the podocyte's production of TGF-1 ligand; rather, it increased the expression of the TGF- type II receptor and activated the TGF- signalling system through Smad2. Despite the TGF- receptor upregulation, synergy between AngII and TGF-1 to boost 3(IV) collagen production was not observed. However, blockade of TGF- signalling with SB-431542 prevented AngII from stimulating 3(IV) collagen production. Podocyte expression of 3(IV) collagen was also increased by the autocrine activity of VEGF. Podocytes were stimulated to secrete VEGF by 10-10 M or higher AngII after 48 h. Blockade of the endogenous VEGF activity by SU5416 prevented AngII-stimulated 3(IV) collagen production.3(IV) collagen protein via mechanisms involving TGF- and VEGF signalling. Alterations in 3(IV) collagen production may contribute to GBM thickening and perhaps proteinuria in diabetes. type II receptor.
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