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

Brian Rooney, Helen O'Donovan, Andrew Gaffney, Marie Browne, Noel Faherty, Simon P. Curran, Denise Sadlier, Catherine Godson, Derek P. Brazil, John Crean*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)531-538
Number of pages8
JournalFEBS Letters
Volume585
Issue number3
DOIs
Publication statusPublished - 04 Feb 2011

Keywords

  • β-Catenin
  • Connective tissue growth factor
  • Diabetic nephropathy
  • Glycogen synthase kinase 3β
  • LRP6
  • Wnt

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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