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

Hideki Kato, Antje Gruenwald, Jung Hee Suh, Jeffrey H. Miner, Laura Barisoni-Thomas, Makoto M. Taketo, Christian H Faul, Sarah E. Millar, Lawrence B. Holzman, Katalin Susztak

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105 Scopus citations

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/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 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.

Original languageEnglish
Pages (from-to)26003-26015
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number29
DOIs
StatePublished - Jul 22 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Kato, H., Gruenwald, A., Suh, J. H., Miner, J. H., Barisoni-Thomas, L., Taketo, M. M., Faul, C. H., Millar, S. E., Holzman, L. B., & Susztak, K. (2011). Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival. Journal of Biological Chemistry, 286(29), 26003-26015. https://doi.org/10.1074/jbc.M111.223164