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CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy
Author(s) -
Rooney Brian,
O‧Donovan Helen,
Gaffney Andrew,
Browne Marie,
Faherty Noel,
Curran Simon P.,
Sadlier Denise,
Godson Catherine,
Brazil Derek P.,
Crean John
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.01.004
Subject(s) - wnt signaling pathway , lrp6 , ctgf , diabetic nephropathy , phosphorylation , catenin , pathogenesis , beta catenin , endocrinology , chemistry , microbiology and biotechnology , medicine , lrp5 , cancer research , signal transduction , biology , diabetes mellitus , growth factor , receptor
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.