1. NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-β1/SMADs Pathway.
- Author
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Guan, Yadi, Tan, Yue, Liu, Weiyu, Yang, Jun, Wang, Dongxu, Pan, Di, Sun, Yan, and Zheng, Changqing
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FIBROSIS , *ANIMAL models in research , *CROHN'S disease , *TRINITROBENZENE , *SULFONIC acids , *DIAGNOSIS , *PROTEIN metabolism , *RESEARCH , *PHENOLS , *FIBROBLASTS , *GROWTH factors , *NUCLEAR factor E2 related factor , *ANIMAL experimentation , *RESEARCH methodology , *EVALUATION research , *CELLULAR signal transduction , *COMPARATIVE studies , *GENES , *RESEARCH funding , *REACTIVE oxygen species , *COLITIS , *CELL lines , *CARRIER proteins , *MICE - 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 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.Conclusions: The results suggested that Nrf2 suppressed intestinal fibrosis by inhibiting ROS/TGF-β1/SMADs pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]- Published
- 2018
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