Abstract

Peroxisome proliferator-activated receptor (PPARγ) has been shown to have a protective role in the nephron through its ability to inhibit a transforming growth factor- (TGF-β) mediated fibrotic response. In contrast, PPARγ 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 5–10 μM troglitazone for 24 hours. Troglitazone resulted in an elongated morphology, 60% decreases in E-cadherin and β-catenin, a 35% decrease in α-catenin, and a 1.5-fold increase in fibronectin. These effects were not reversed with PPARγ antagonists or affected with PPARγ overexpression. Our results indicate that troglitazone induced a mesenchymal-like transformation in M1 and IMCD-K2 epithelial cells independently of PPARγ.

Highlights

  • PPARs are ligand-activated transcription factors that heterodimerize with an RXR receptor

  • We report that TGF-β was unable to initiate an epithelial to mesenchymal transformation in the IMCD-K2 and M1 collecting duct cell lines

  • PPARγ is present in the collecting duct; the use of TRO, a potent synthetic ligand, resulted in structural changes independent of its target receptor

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Summary

Introduction

PPARs are ligand-activated transcription factors that heterodimerize with an RXR receptor. PPARγ activation by TZDs has been shown to result in oedema through enhanced epithelial sodium cotransporter (ENaC) activity in the CD [6]. These effects were blocked by amiloride, a CD-specific diuretic. Whether PPARγ is an antifibrotic transcription factor is unclear as there have been studies indicating an induction of fibrotic responses by PPARγ ligands. An example of this was found in the intestine where activation of PPARγ was shown to induce a mesenchymal transition in epithelial intestinal cell line [7]

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