NDT Advance Access originally published online on January 8, 2008
Nephrology Dialysis Transplantation 2008 23(6):1844-1853; doi:10.1093/ndt/gfm917
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Deletion of MK2 signalling in vivo inhibits small Hsp phosphorylation but not diabetic nephropathy
1 Department of Nephrology 2 Department of Biochemistry, Hannover Medical School, Hannover, Germany
Correspondence and offprint requests to: Correspondence and offprint requests to: Matthias Meier, Medical School Hannover, Carl-Neuberg Street 1, 30625 Hannover, Germany. Tel: +49-511-5323669; Fax: +49-511-552366; E-mail: KfNH_Hannover{at}web.de
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Abstract |
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It is supposed that some stress-induced heat shock proteins (Hsps) are regulated through e.g. stimulation of the p38MAPK/MK(MAPKAP)-2 signalling pathway. It has been postulated from in vitro experiments that phosphorylation of Hsp25(rodents)/Hsp27(human), the major phosphorylation substrate of MK2, is responsible for mesangial contractility and glomerular hyperfiltration in the diabetic kidney. To verify this hypothesis in vivo we studied the renal function of nondiabetic and streptozotocin (STZ)-induced, diabetic MK2–/– mice in comparison to wild-type (WT) control mice. Following 8 weeks of hyperglycaemia, light microscopy showed increased glomerulosclerosis and tubulointerstitial renal fibrosis in both diabetic study groups. Protein analysis demonstrated that Hsp25 phosphorylation is stimulated upon high-glucose condition but inhibited in the diabetic MK2–/– mice. However, we found the kidney–body weight ratio significantly increased in diabetic WT and MK2–/– mice. No difference regarding the increased expression of the extracellular matrix proteins and TGF-β1 between both diabetic study groups was observed. Importantly, diabetic MK2–/– mice showed no protection against renal hyperfiltration in the diabetic state and the development of diabetic albuminuria. Although activation of p38MAPK has been previously shown in diabetes mellitus, our results indicate that blockade of the downstream MK2/Hsp25 signalling pathway does not interfere with the development of early diabetic nephropathy.
Keywords: diabetic nephropathy; heat shock protein (Hsp); MK2
Received for publication: 5. 2.07
Accepted in revised form: 6.12.07
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  F. Barutta, S. Pinach, S. Giunti, F. Vittone, J. M. Forbes, R. Chiarle, M. Arnstein, P. C. Perin, G. Camussi, M. E. Cooper, et al. Heat shock protein expression in diabetic nephropathy Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1817 - F1824. [Abstract] [Full Text] [PDF]
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