Curcumin Suppresses Intestinal Fibrosis by Inhibition of PPAR<i>γ</i>‐Mediated Epithelial‐Mesenchymal Transition

Abstract

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 <i>Curcuma</i>, 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-<i>β</i>1-induced Smad pathway and decreases its downstream <i>α</i>-smooth muscle actin (<i>α</i>-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptor <i>γ</i> (PPAR<i>γ</i>) in IEC-6. Moreover, curcumin promotes nuclear translocation of PPAR<i>γ</i> and the inhibitory effect of curcumin on EMT could be reversed by PPAR<i>γ</i> 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<i>γ</i> and E-cadherin and decreasing the expression of <i>α</i>-SMA, FN, and CTGF in colon tissue. Collectively, these results indicated that curcumin is able to prevent EMT progress in intestinal fibrosis by PPAR<i>γ</i>-mediated repression of TGF-<i>β</i>1/Smad pathway.