The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis

Citations Over TimeTop 10% of 2016 papers

Abstract

Renal tubulointerstitial fibrosis (TIF) is the final pathway of various renal injuries that result in chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the regulation of cell proliferation, cell death, tissue regeneration, and tumorigenesis. Here, we report that the Hippo-Salvador pathway plays a role in disease development in patients with TIF and in a mouse model of TIF. Mice with tubular epithelial cell (TEC)-specific deletions of Sav1 (Salvador homolog 1) exhibited aggravated renal TIF, enhanced epithelial-mesenchymal transition-like phenotypic changes, apoptosis, and proliferation after unilateral ureteral obstruction (UUO). Moreover, Sav1 depletion in TECs increased transforming growth factor (TGF)-β and activated β-catenin expression after UUO, which likely accounts for the abovementioned enhanced TEC fibrotic phenotype. In addition, TAZ (transcriptional coactivator with PDZ-binding motif), a major downstream effector of the Hippo pathway, was significantly activated in Sav1-knockout mice in vivo. An in vitro study showed that TAZ directly regulates TGF-β and TGF-β receptor II expression. Collectively, our data indicate that the Hippo-Salvador pathway plays a role in the pathogenesis of TIF and that regulating this pathway may be a therapeutic strategy for reducing TIF.

Related Papers

• → Role of the Hippo pathway and mechanisms for controlling cellular localization of YAP/TAZ(2021)89 cited
• → [Research advances in the role of the Hippo signaling pathway in pathogenesis of liver cancer].(2017)2 cited
• → The Hippo–YAP pathway in organ size control and tumorigenesis: an updated version(2010)1,133 cited
• → Abstract IA04: Regulation of the Hippo pathway in cancer(2020)
• → P04.20 The role of YAP in Glioblastoma cell lines(2021)