|作者：||Guan Yadi, Tan Yue, Liu Weiyu, Yang Jun, Wang Dongxu, Pan Di, Sun Yan, Zheng Changqing|
1Department of Gastroenterology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Tiexi District, Shenyang, 110022, Liaoning Province, China.
2Department of Gastroenterology, The People's Hospital Liaoning Provincial, 33 Wenyi Road, Shenhe District, Shenyang, 110013, Liaoning Province, China.
3Department of Gastroenterology, Shengjing Hospital of China Medical Universit
|刊名：||Digestive diseases and sciences, 2018, Vol.63 (2), pp.366-380|
|关键词：||Colitis; Fibrosis; NF-E2-Related Factor 2; Reactive oxygen species; TGF-β1/SMADs signaling pathway;|
|原始语种摘要：||BACKGROUND AND AIMS(#br)This study aimed to evaluate the antifibrotic effects of NF-E2-Related Factor 2 (Nrf2) on intestinal fibrosis. Intestinal fibrosis is a common complication of Crohn's disease; however, its mechanism of intestinal fibrosis is largely unclear.(#br)METHODS(#br)BALB/c mice received 2,4,6-trinitrobenzene sulfonic acid weekly via intrarectal injections to induce chronic fibrotic colitis. They also diet containing received 1% (w/w) tert-butylhydroquinone (tBHQ), which is an agonist of Nrf2. Human intestinal fibroblasts (CCD-18Co cells) were pretreated with tBHQ or si-Nrf2 followed by stimulation with transforming growth factor-β1 (TGF-β1), which transformed the cells into myofibroblasts. The main fibrosis markers such as α-smooth muscle actin, collagen I, tissue inhibitor... of metalloproteinase-1, and TGF-β1/SMADs signaling pathway were detected by quantitative real-time RT-PCR, immunohistochemical analysis, and Western blot analysis. Levels of cellular reactive oxygen species (ROS) were detected by dichlorodihydrofluorescein diacetate.(#br)RESULTS(#br)tBHQ suppressed the intestinal fibrosis through the TGF-β1/SMADs signaling pathway in TNBS-induced colitis and CCD-18Co cells. Moreover, Nrf2 knockdown enhanced the TGF-β1-induced differentiation of CCD-18Co cells. ROS significantly increased in TGF-β1-stimulated CCD-18Co cells. Pretreatment with H2O2, the primary component of ROS, was demonstrated to block the effect of tBHQ on reducing the expression of TGF-β1. Moreover, scavenging ROS by N-acetyl cysteine could inhibit the increasing expression of TGF-β1 promoted by Nrf2 knockdown.(#br)CONCLUSIONS(#br)The results suggested that Nrf2 suppressed intestinal fibrosis by inhibiting ROS/TGF-β1/SMADs pathway in vivo and in vitro.|