Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD.

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) can be caused by mutations in the PKD1 or PKD2 genes. The PKD1 gene product is a Wnt cell-surface receptor. We previously showed that a lack of the PKD2 gene product, PC2, increases β-catenin signaling in mouse embryonic fibroblasts, kidney renal epithelia, and isolated renal collecting duct cells. However, it remains unclear whether β-catenin signaling plays a role in polycystic kidney disease phenotypes or if a Wnt inhibitor can halt cyst formation in ADPKD disease models. Here, using genetic and pharmacologic approaches, we demonstrated that the elevated β-catenin signaling caused by PC2 deficiency contributes significantly to disease phenotypes in a mouse ortholog of human ADPKD. Pharmacologically inhibiting β-catenin stability or th

SUBMITTER: Li A 

PROVIDER: S-EPMC5922276 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature