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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/F1817    most recent 90234.2008v1 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 Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Barutta, F. Articles by Gruden, G. Search for Related Content PubMed PubMed Citation Articles by Barutta, F. Articles by Gruden, G.

Heat shock protein expression in diabetic nephropathy

¹Diabetic Nephropathy Laboratory, Department of Internal Medicine, and ³Department of Biomedical Sciences and Human Oncology and Research Center on Experimental Medicine (CeRMS), University of Turin, Turin, Italy; and ²Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Diabetes Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

Submitted 2 April 2008 ; accepted in final form 10 October 2008

Heat shock protein (HSP) HSP27, HSP60, HSP70, and HSP90 are induced by cellular stresses and play a key role in cytoprotection. Both hyperglycemia and glomerular hypertension are crucial determinants in the pathogenesis of diabetic nephropathy and impose cellular stresses on renal target cells. We studied both the expression and the phosphorylation state of HSP27, HSP60, HSP70, and HSP90 in vivo in rats made diabetic with streptozotocin and in vitro in mesangial cells and podocytes exposed to either high glucose or mechanical stretch. Diabetic and control animals were studied 4, 12, and 24 wk after the onset of diabetes. Immunohistochemical analysis revealed an overexpression of HSP25, HSP60, and HSP72 in the diabetic outer medulla, whereas no differences were seen in the glomeruli. Similarly, exposure neither to high glucose nor to stretch altered HSP expression in mesangial cells and podocytes. By contrast, the phosphorylated form of HSP27 was enhanced in the glomerular podocytes of diabetic animals, and in vitro exposure of podocytes to stretch induced HSP27 phosphorylation via a P38-dependent mechanism. In conclusion, diabetes and diabetes-related insults differentially modulate HSP27, HSP60, and HSP70 expression/phosphorylation in the glomeruli and in the medulla, and this may affect the ability of renal cells to mount an effective cytoprotective response.

mesangial cells; glomerular epithelial cells; mechanical stretch