title: Curcumin Suppresses Intestinal Fibrosis by Inhibition of PPARγ-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 ofCurcuma, 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-β1-induced Smad pathway and decreases its downstreamα-smooth muscle actin (α-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptorγ(PPARγ) in IEC-6. Moreover, curcumin promotes nuclear translocation of PPARγand the inhibitory effect of curcumin on EMT could be reversed by PPARγantagonist 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 PPARγand E-cadherin and decreasing the expression ofα-SMA, FN, and CTGF in colon tissue. Collectively, these results indicated that curcumin is able to prevent EMT progress in intestinal fibrosis by PPARγ-mediated repression of TGF-β1/Smad pathway.
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, China; Department of Colorectal Surgery, The Yancheng Affiliated Hospital of Nanjing University of Chinese Medicine, No. 53 People's Road, Yancheng 224001, China.
authors.forename: Su
authors.identifier: 0000-0002-5970-8172
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Colorectal Surgery, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, No. 1 Jinling Road, Nanjing 210001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, China.
authors.forename: Cunsi
authors.initials: C
authors.lastname: Shen
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: First Clinical Medical College, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Nanjing 210023, China.
authors.forename: Li
authors.identifier: 0000-0002-9095-9439
authors.initials: L
authors.lastname: Zeng