WNT/ β-catenin signal inhibitor IC-2-derived small-molecule compounds suppress TGF-β1-induced fibrogenic response of renal epithelial cells by inhibiting SMAD2/3 signaling.

WNT/β-catenin signal inhibitor IC-2-derived small-molecule compounds suppress TGF-β1-induced fibrogenic response of renal epithelial cells by inhibiting SMAD2/3 signaling.
Clin Exp Pharmacol Physiol. 2020 Feb 03;:
Authors: Hoi S, Tsuchiya H, Itaba N, Suzuki K, Oka H, Morimoto M, Takata T, Isomoto H, Shiota G
Abstract
Renal fibrosis compromises kidney function, and it is a risk factor for chronic kidney disease (CKD). CKD ultimately progresses to end-stage kidney disease that can be cured only by kidney transplantation. Owing to the increasing number of CKD patients, effective treatment strategies are urgently required for renal fibrosis. TGF-β is a well-established fibrogenic factor that signals through SMAD2/3 signaling pathway. It was shown that there is a cross-talk between TGF-β/SMAD and WNT/β-catenin signaling pathways in renal tubular epithelial cells, and that a WNT/β-catenin inhibitor, ICG-001, ameliorates TGF-β1induced renal fibrosis. IC-2, a derivative of ICG-001, has been shown to potently induce hepatocyte differentiation of human mesenchymal stem cells by inhibiting WNT/β-catenin signaling. In the present study, we examined the effect of ICG-001, IC-2, and IC-2 derivatives (IC-2-506-1, IC-2-506-2, IC-2-506-3, IC-2-Ar-Cl, IC-2-OH, IC-2-OTBS, and IC-2-F) on TGF-β1-induced SMAD activation and fibrogenic response in immortalized human renal tubular epithelial HK-2 cells. All these compounds inhibited LiCl-induced WN...

Source: Clinical and Experimental Pharmacology and Physiology - February 2, 2020 Category: Drugs & Pharmacology Authors: Hoi S, Tsuchiya H, Itaba N, Suzuki K, Oka H, Morimoto M, Takata T, Isomoto H, Shiota G Tags: Clin Exp Pharmacol Physiol Source Type: research