Curcumin Suppresses Intestinal Fibrosis by Inhibition of PPAR-Mediated Epithelial-Mesenchymal Transition.

Intestinal fibrotic stricture is a major complication of Crohn's disease (CD) and epithelial-to-mesenchymal transition (EMT) is considered as an important contributor to the formation of intestinal fibrosis by increasing extracellular matrix (ECM) proteins. Curcumin, a compound derived from rhizomes of , has been demonstrated with a potent antifibrotic effect. However, its effect on intestinal fibrosis and the potential mechanism is not completely understood. Here we found that curcumin pretreatment significantly represses TGF-1-induced Smad pathway and decreases its downstream -smooth muscle actin (-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptor (PPAR) in IEC-6. Moreover, curcumin promotes nuclear translocation of PPAR and the inhibitory effect of curcumin on EMT could be reversed by PPAR antagonist GW9662. Consistently, in the rat model of intestinal fibrosis induced by 2,4,5-trinitrobenzene sulphonic acid (TNBS), oral curcumin attenuates intestinal fibrosis by increasing the expression of PPAR and E-cadherin and decreasing the expression of -SMA, FN, and CTGF in colon tissue. Collectively, these results indicated that curcumin is able to prevent EMT progress in intestinal fibrosis by PPAR-mediated repression of TGF-1/Smad pathway.