β-Catenin Causes Renal Dysplasia via Upregulation of Tgfβ2 and Dkk1

被引：35

作者：

Bridgewater, Darren ^{[1
,2
]}

Di Giovanni, Valeria ^{[1
,2
,3
]}

Cain, Jason E. ^{[1
,2
]}

Cox, Brian ^{[2
]}

Jakobson, Madis ^{[4
]}

Sainio, Kirsi ^{[4
]}

Rosenblum, Norman D. ^{[1
,2
,3
]}

机构：

[1] Hosp Sick Children, Div Nephrol, Toronto, ON M5G 1X8, Canada

[2] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada

[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[4] Univ Helsinki, Inst Biomed, Helsinki, Finland

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2011年 / 22卷 / 04期

基金：

加拿大健康研究院;

关键词：

MICE LACKING GDNF; KIDNEY DEVELOPMENT; URETERAL BUD; TRANSGENIC MICE; EPITHELIAL TRANSFORMATION; METANEPHRIC MESENCHYME; LACZ EXPRESSION; DISEASE; CELLS; MOUSE;

D O I：

10.1681/ASN.2010050562

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Renal dysplasia, defined by defective ureteric branching morphogenesis and nephrogenesis, is the major cause of renal failure in infants and children. Here, we define a pathogenic role for a beta-catenin-activated genetic pathway in murine renal dysplasia. Stabilization of beta-catenin in the ureteric cell lineage before the onset of kidney development increased beta-catenin levels and caused renal aplasia or severe hypodysplasia. Analysis of gene expression in the dysplastic tissue identified downregulation of genes required for ureteric branching and upregulation of Tgf beta 2 and Dkk1. Treatment of wild-type kidney explants with TGF beta 2 or DKK1 generated morphogenetic phenotypes strikingly similar to those observed in mutant kidney tissue. Stabilization of p-catenin after the onset of kidney development also caused dysplasia and upregulation of Tgf beta 2 and Dkk1 in the epithelium. Together, these results demonstrate that elevation of p-catenin levels during kidney development causes dysplasia.

引用

页码：718 / 731

页数：14

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