Canonical Wnt/β-catenin signaling mediates transforming growth factor-β1-driven podocyte injury and proteinuria.

ABSTRACT: Transforming growth factor-β1 (TGF-β1) upregulation occurs in virtually all chronic kidney diseases and is associated with podocyte injury and proteinuria; however, the mechanisms contributing to this in vivo are ambiguous. In vitro, incubation of podocytes with TGF-β1 induced Wnt1 expression, β-catenin activation, and stimulated the expression of Wnt/β-catenin downstream target genes. Ectopic expression of Wnt1 or β-catenin mimicked TGF-β1, induced Snail1, and suppressed nephrin expression. The Wnt antagonist, Dickkopf-1, blocked TGF-β1-induced β-catenin activation, Snail1 induction, and nephrin suppression. In vivo, ectopic expression of TGF-β1 induced Wnt1 expression, activated β-catenin, and upregulated Wnt target genes such as Snail1, MMP-7, MMP-9, desmin, Fsp1, and PAI-1 in mouse glo

SUBMITTER: Wang D 

PROVIDER: S-EPMC4300105 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature