CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: implications for the pathogenesis of diabetic nephropathy.

UCD Diabetes Research Centre, UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland.
FEBS letters (Impact Factor: 3.54). 02/2011; 585(3):531-8. DOI: 10.1016/j.febslet.2011.01.004
Source: PubMed

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.

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