%0 Journal Article
%T Curcumin Inhibits Transforming Growth Factor-¦Â1-Induced EMT via PPAR¦Ã Pathway, Not Smad Pathway in Renal Tubular Epithelial Cells
%A Rui Li
%A Yunman Wang
%A Yujun Liu
%A Qijing Chen
%A Wencheng Fu
%A Hao Wang
%A Hui Cai
%A Wen Peng
%A Xuemei Zhang
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0058848
%X 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 ¦Á-SMA and PAI-1, and increased E-cadherin in TGF-¦Â1 treated proximal tubular epithelial cell HK-2 cells. Both of the conventional TGF-¦Â1/Smad pathway and non-Smad pathway were investigated. Curcumin reduced TGF-¦Â receptor type I (T¦ÂR-I) and TGF-¦Â receptor type II (T¦ÂR II), but had no effect on phosphorylation of Smad2 and Smad3. On the other hand, in non-Smad pathway curcumin reduced TGF-¦Â1-induced ERK phosphorylation and PPAR¦Ã phosphorylation, and promoted nuclear translocation of PPAR¦Ã. Further, the effect of curcumin on ¦Á-SMA, PAI-1, E-cadherin, T¦ÂR I and T¦ÂR II were reversed by ERK inhibitor U0126 or PPAR¦Ã inhibitor BADGE, or PPAR¦Ã shRNA. Blocking PPAR¦Ã 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 PPAR¦Ã. We conclude that curcumin counteracted TGF-¦Â1-induced EMT in renal tubular epithelial cells via ERK-dependent and then PPAR¦Ã-dependent pathway.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058848