| Literature DB >> 21237163 |
Brian Rooney1, Helen O'Donovan, Andrew Gaffney, Marie Browne, Noel Faherty, Simon P Curran, Denise Sadlier, Catherine Godson, Derek P Brazil, John Crean.
Abstract
We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of β-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. β-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.Entities:
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Year: 2011 PMID： 21237163 DOI： 10.1016/j.febslet.2011.01.004
Source DB: PubMed Journal: FEBS Lett ISSN： 0014-5793 Impact factor: 4.124