Submitted on April 2, 2008
Revised on September 23, 2008
Accepted on October 10, 2008
Heat Shock Protein Expression In Diabetic Nephropathy
Federica Barutta1*, Silvia Pinach, Sara Giunti, Ferdinando Vittone, Josephine M. Forbes2, Roberto Chiarle1, Maryann Arnstein, Paolo Cavallo Perin, Giovanni Camussi3, Mark E Cooper4, and Gabriella Gruden
1 University of Turin
2 Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute
3 Universita di Torino
4 University of Melbourne
* To whom correspondence should be addressed. E-mail: fede.barutta{at}libero.it.
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 upon 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 weeks 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, neither exposure 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.
