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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/F1641    most recent 00179.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Mitu, G. M. Articles by Hirschberg, R. Search for Related Content PubMed PubMed Citation Articles by Mitu, G. M. Articles by Hirschberg, R.

BMP7 is a podocyte survival factor and rescues podocytes from diabetic injury

Los Angeles Biomedical Research Institute (LABioMed) at Harbor-UCLA Medical Center, Torrance, California

Submitted 15 April 2007 ; accepted in final form 4 September 2007

In early diabetic renal injury, there is podocyte drop-out (but no decrease in the number of other glomerular cells) which is thought to cause glomerular proteinuria and subsequent diabetic glomerular injury. We tested the hypothesis that early diabetic podocyte injury is caused, in part, by downregulation of bone morphogenetic protein-7 (BMP7) and loss of its autocrine function in murine podocytes. High glucose (HG; 25 mM) induces rounding of differentiated podocytes and changes in the distribution of F-actin but without quantitative changes in E-cadherin and the podocyte markers podocin, CD2AP, Neph1, or synaptopodin. HG reduces BMP7 secretion and activity but does not affect BMP receptor levels in murine podocytes. In these cells, BMP7 effectively activates smad5 (but not smad1) and raises p38 phosphorylation [which is also increased by transforming growth factor- (TGF-)]. HG as well as TGF- raise caspase-3 activity, increase apoptosis, and reduce cell survival which is, in part, blocked by BMP7. Knockdown and forced expression studies indicate that smad5 is required as well as sufficient for these actions of BMP7. These findings indicate that BMP7 is a differentiation and survival factor for podocytes, requires smad5, and can reduce diabetic podocyte injury.

diabetic nephropathy; apoptosis; smad; caspase-3

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