Journal Article

Deletion of MK2 signalling <i>in vivo</i> inhibits small Hsp phosphorylation but not diabetic nephropathy

Joon-Keun Park, Natalia Ronkina, Andreas Höft, Corinna Prohl, Jan Menne, Matthias Gaestel, Hermann Haller and Matthias Meier

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 6, pages 1844-1853
Published in print June 2008 | ISSN: 0931-0509
Published online January 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfm917
Deletion of MK2 signalling in vivo inhibits small Hsp phosphorylation but not diabetic nephropathy

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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

Journal Article.  4772 words.  Illustrated.

Subjects: Nephrology

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