Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, S.
Right arrow Articles by Ziyadeh, F. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, S.
Right arrow Articles by Ziyadeh, F. N.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:2939-2949, 2004
© 2004 by the American Diabetes Association, Inc.

Podocyte-Derived Vascular Endothelial Growth Factor Mediates the Stimulation of {alpha}3(IV) Collagen Production by Transforming Growth Factor-ß1 in Mouse Podocytes

Sheldon Chen, Yuki Kasama, Joseph S. Lee, Belinda Jim, Maria Marin, and Fuad N. Ziyadeh

From the Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Podocyte-derived vascular endothelial growth factor (VEGF) is upregulated in diabetes and may contribute to albuminuria. Although believed to act upon the glomerular endothelium, VEGF may have pronounced effects on the podocyte itself. The functionality of this VEGF autocrine loop was investigated in conditionally immortalized mouse podocytes. Exogenous VEGF164 increased the production of {alpha}3(IV) collagen, an integral component of the glomerular basement membrane (GBM); this effect was completely prevented by SU5416, a pan-VEGF receptor inhibitor. The VEGF inhibitor also partially prevented the stimulation of {alpha}3(IV) collagen by transforming growth factor (TGF)-ß1, establishing a novel role for endogenous VEGF. However, VEGF did not influence the production of another novel chain of collagen IV, {alpha}5(IV) collagen, and SU5416 failed to reverse the known inhibitory effect of TGF-ß1 on {alpha}5(IV) collagen production. Cultured mouse podocytes possess at least the VEGFR-1 receptor, confirmed by RT-PCR, immunoblotting, and immunocytochemistry. By these techniques, however, VEGFR-2 is absent. VEGF signaling proceeds via autophosphorylation of VEGFR-1 and activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Thus, podocyte-derived VEGF operates in an autocrine loop, likely through VEGFR-1 and PI3K, to stimulate {alpha}3(IV) collagen production. The TGF-ß1–stimulated endogenous VEGF may have significant implications for podocyte dysfunction in diabetic glomerulopathy, manifesting as GBM thickening and altered macromolecular permeability.

Address correspondence and reprint requests to Sheldon Chen, MD, 700 Clinical Research Building, 415 Curie Blvd., Philadelphia, Pennsylvania 19104-4218. E-mail: chens{at}mail.med.upenn.edu


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.