Troglitazone induces extracellular matrix and cytoskeleton remodeling in mouse collecting duct cells

Abstract

Peroxisome proliferator-activated receptor (PPAR) has been shown to have a protective role in the nephron through its ability to inhibit a transforming growth factor- (TGF-) mediated fibrotic response. In contrast, PPAR was also shown to induce a mesenchymal transformation in epithelial intestinal cells. A fibrotic response in the collecting duct has only recently been established; however, the entire collecting duct has not been fully examined. Inner medullary collecting duct cells (IMCD-K2) and mouse cortical collecting duct cells (M1), representing the cortical and medullary collecting duct, were exposed to 510M troglitazone for 24 hours. Troglitazone resulted in an elongated morphology, 60 decreases in E-cadherin and -catenin, a 35 decrease in -catenin, and a 1.5-fold increase in fibronectin. These effects were not reversed with PPAR antagonists or affected with PPAR overexpression. Our results indicate that troglitazone induced a mesenchymal-like transformation in M1 and IMCD-K2 epithelial cells independently of PPAR. Copyright © 2012 Jaime Corinaldi et al.