Premium
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom