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Wnt/?-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival.

ABSTRACT: Diabetic kidney disease (DKD) is the single most common cause of albuminuria and end-stage kidney disease in the United States. We found increased expression of Wnt/?-catenin (Ctnnb1) pathway transcripts and proteins in glomeruli and podocytes of patients and mouse models of DKD. Mice with podocyte-specific expression of stabilized Ctnnb1 exhibited basement membrane abnormalities, albuminuria, and increased susceptibility to glomerular injury. Mice with podocyte-specific deletion of Ctnnb1 or podocyte-specific expression of the canonical Wnt inhibitor Dickkopf-related protein 1 (Dkk1) also showed increased susceptibility to DKD. Podocytes with stabilized Ctnnb1 were less motile and less adhesive to different matrices. Deletion of Ctnnb1 in cultured podocytes increased the expression of podocyte differentiation markers and enhanced cell motility; however, these cells were more susceptible to apoptosis. These results indicate that Wnt/Ctnnb1 signaling in podocytes plays a critical role in integrating cell adhesion, motility, cell death, and differentiation. Balanced Ctnnb1 expression is critical for glomerular filtration barrier maintenance.

SUBMITTER: Kato H

PROVIDER: S-EPMC3138306 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival.

Kato Hideki H Gruenwald Antje A Suh Jung Hee JH Miner Jeffrey H JH Barisoni-Thomas Laura L Taketo Makoto M MM Faul Christian C Millar Sarah E SE Holzman Lawrence B LB Susztak Katalin K

The Journal of biological chemistry 20110525 29

Diabetic kidney disease (DKD) is the single most common cause of albuminuria and end-stage kidney disease in the United States. We found increased expression of Wnt/β-catenin (Ctnnb1) pathway transcripts and proteins in glomeruli and podocytes of patients and mouse models of DKD. Mice with podocyte-specific expression of stabilized Ctnnb1 exhibited basement membrane abnormalities, albuminuria, and increased susceptibility to glomerular injury. Mice with podocyte-specific deletion of Ctnnb1 or po ...[more]

PMID: 21613219

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Wnt/?-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival.

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Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival.

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