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

doi:10.1016/j.febslet.2011.01.004

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 journal › Article › peer-review

69 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 language	English
Pages (from-to)	531-538
Number of pages	8
Journal	FEBS Letters
Volume	585
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2011.01.004
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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

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.",

keywords = "β-Catenin, Connective tissue growth factor, Diabetic nephropathy, Glycogen synthase kinase 3β, LRP6, Wnt",

author = "Brian Rooney and Helen O'Donovan and Andrew Gaffney and Marie Browne and Noel Faherty and Curran, {Simon P.} and Denise Sadlier and Catherine Godson and Brazil, {Derek P.} and John Crean",

year = "2011",

month = feb,

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doi = "10.1016/j.febslet.2011.01.004",

language = "English",

volume = "585",

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journal = "FEBS Letters",

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TY - JOUR

T1 - CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: implications for the pathogenesis of diabetic nephropathy

AU - Rooney, Brian

AU - O'Donovan, Helen

AU - Gaffney, Andrew

AU - Browne, Marie

AU - Faherty, Noel

AU - Curran, Simon P.

AU - Sadlier, Denise

AU - Godson, Catherine

AU - Brazil, Derek P.

AU - Crean, John

PY - 2011/2/4

Y1 - 2011/2/4

N2 - 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.

AB - 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.

KW - β-Catenin

KW - Connective tissue growth factor

KW - Diabetic nephropathy

KW - Glycogen synthase kinase 3β

KW - LRP6

KW - Wnt

U2 - 10.1016/j.febslet.2011.01.004

DO - 10.1016/j.febslet.2011.01.004

M3 - Article

C2 - 21237163

AN - SCOPUS:79551483244

SN - 0014-5793

VL - 585

SP - 531

EP - 538

JO - FEBS Letters

JF - FEBS Letters

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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