Troglitazone induces extracellular matrix & cytoskeleton remodeling in the IMCD-K2 & M1 renal collecting duct cell lines

Abstract

TGF-beta activation has been inhibited with Troglitazone, a synthetic PPARgamma ligand (Peng, Liu et al. 2006). The fibrotic response in the collecting ducts of the nephron, particularly in terms of EMT, has only recently been established (Ivanova, Butt et al. 2008). The purpose of this study was to characterize a fibrotic response in the collecting duct with TGF-beta and to assess PPARgamma's role in the phenomenon. We hypothesized PPARgamma activation will have a protective effect in the collecting duct, preventing TGF-beta mediated EMT. TGF-beta was unable to initiate a fibrotic response in the IMCD-K2 & M1 collecting duct cell lines. In contrast, Troglitazone caused morphological changes and decreases in E-cadherin, alpha-catenin & beta-catenin, as well as an increase in fibronectin. These effects were not reversed with PPARgamma antagonists or a GSK-3beta blocker. Troglitazone induced a transformation in M1 & IMCD-K2 cells independently of PPARgamma.