TAZ/Wnt-β-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease
Eun Ji Lee, Eunjeong Seo, Jin Won Kim, Sun Ah Nam, Jong‐Young Lee, Jaehee Jun, Sumin Oh, Minah Park, Eek‐hoon Jho, Kyung Hyun Yoo, Jong Hoon Park, Yong Kyun Kim
Abstract
Significance Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, primarily caused by germline mutation of PKD1 or PKD2 , leading to end-stage renal disease. There are few cures for ADPKD, although many researchers are trying to find a cure. The Hippo signaling pathway regulates organ growth and cell proliferation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a Hippo signaling effector. In this study, we demonstrated that the PKD1–TAZ–Wnt–β-catenin–c-MYC signaling axis plays a critical role in cystogenesis. Endo IWR1 treatment, which inhibited β-catenin activity via AXIN stabilization, reduced cyst growth in an ADPKD model. Our findings provide a potential therapeutic target against ADPKD and would be important for clinical translation.