Journal
FEBS LETTERS
Volume 585, Issue 3, Pages 531-538Publisher
WILEY
DOI: 10.1016/j.febslet.2011.01.004
Keywords
Connective tissue growth factor; Wnt; Glycogen synthase kinase 3 beta; beta-Catenin; LRP6; Diabetic nephropathy
Funding
- Science Foundation Ireland
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We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3 beta resulting in accumulation and nuclear localisation of beta-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of beta-catenin on Ser 33/37 and increased phosphorylation on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2's effects. Microarray analyses of diabetic patients identified differentially expressed Wnt components. beta-Catenin is increased in type 1 diabetic and UUO mice and in in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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