Curcumin Inhibits Transforming Growth Factor-beta 1-Induced EMT via PPAR gamma Pathway, Not Smad Pathway in Renal Tubular Epithelial Cells

• Type of Material: Article
• Authors: Rui Li, Fudan University; Yunman Wang, Shanghai University of Traditional Chinese Medicine; Yujun Liu, Shanghai University of Traditional Chinese Medicine; Qijing Chen, Fudan University; Wencheng Fu, Shanghai University of Traditional Chinese Medicine; Hao Wang, Shanghai University of Traditional Chinese Medicine; Hui Cai, Emory University; Wen Peng, Shanghai University of Traditional Chinese Medicine; Xuemei Zhang, Fudan University
• Language: English
• Date: 2013-03-27
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Li et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0058848
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 3
• Start Page: e58848
• End Page: e58848
• Keywords: Multidisciplinary Sciences; MESENCHYMAL TRANSITION; ACTIVATED-RECEPTOR-GAMMA; MULTIDISCIPLINARY SCIENCES; MULTIPLE SITES; MECHANISMS; RATS; FIBROSIS; Science & Technology; TGF-BETA; GENE-EXPRESSION; Science & Technology - Other Topics; PHOSPHORYLATION; SIGNALING PATHWAYS
• Research Categories: Health Sciences, Pharmacology

Abstract

Tubulointerstitial fibrosis (TIF) is the final common pathway in the end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is considered a major contributor to the TIF by increasing the number of myofibroblasts. Curcumin, a polyphenolic compound derived from rhizomes of Curcuma, has been shown to possess potent anti-fibrotic properties but the mechanism remains elusive. We found that curcumin inhibited the EMT as assessed by reduced expression of α-SMA and PAI-1, and increased E-cadherin in TGF-β1 treated proximal tubular epithelial cell HK-2 cells. Both of the conventional TGF-β1/Smad pathway and non-Smad pathway were investigated. Curcumin reduced TGF-β receptor type I (TβR-I) and TGF-β receptor type II (TβR II), but had no effect on phosphorylation of Smad2 and Smad3. On the other hand, in non-Smad pathway curcumin reduced TGF-β1-induced ERK phosphorylation and PPARγ phosphorylation, and promoted nuclear translocation of PPARγ. Further, the effect of curcumin on α-SMA, PAI-1, E-cadherin, TβR I and TβR II were reversed by ERK inhibitor U0126 or PPARγ inhibitor BADGE, or PPARγ shRNA. Blocking PPARγ signaling pathway by inhibitor BADGE or shRNA had no effect on the phosphorylation of ERK whereas the suppression of ERK signaling pathway inhibited the phosphorylation of PPARγ. We conclude that curcumin counteracted TGF-β1-induced EMT in renal tubular epithelial cells via ERK-dependent and then PPARγ-dependent pathway.