NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-β1/SMADs Pathway

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2017 Aug 18

PMID 28815354

Citations 21

Authors

Yadi Guan

Yue Tan

Weiyu Liu

Jun Yang

Dongxu Wang

Di Pan

Yan Sun

Changqing Zheng

Affiliations

Soon will be listed here.

Abstract

Background And Aims: 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.

Methods: 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.

Results: 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 HO, 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.

Conclusions: The results suggested that Nrf2 suppressed intestinal fibrosis by inhibiting ROS/TGF-β1/SMADs pathway in vivo and in vitro.

Citing Articles

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