Journal
PLOS ONE
Volume 8, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0058848
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Funding
- Natural Science Foundation of Shanghai [11ZR1433200]
- Science Foundation of Shanghai Education Commission [2010JW61]
- Science and Technology of Putuo District, Shanghai [2008PTKW010]
- College of the Shanghai Municipal Education Commission, China
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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 alpha-SMA and PAI-1, and increased E-cadherin in TGF-beta 1 treated proximal tubular epithelial cell HK-2 cells. Both of the conventional TGF-beta 1/Smad pathway and non-Smad pathway were investigated. Curcumin reduced TGF-beta receptor type I (T beta R-I) and TGF-beta receptor type II (T beta R II), but had no effect on phosphorylation of Smad2 and Smad3. On the other hand, in non-Smad pathway curcumin reduced TGF-beta 1-induced ERK phosphorylation and PPAR gamma phosphorylation, and promoted nuclear translocation of PPAR gamma. Further, the effect of curcumin on alpha-SMA, PAI-1, E-cadherin, T beta R I and T beta R II were reversed by ERK inhibitor U0126 or PPAR gamma inhibitor BADGE, or PPAR gamma shRNA. Blocking PPAR gamma 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 gamma. We conclude that curcumin counteracted TGF-beta 1-induced EMT in renal tubular epithelial cells via ERK-dependent and then PPAR gamma-dependent pathway.
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