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NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-β1/SMADs Pathway.
- Source :
-
Digestive Diseases & Sciences . Feb2018, Vol. 63 Issue 2, p366-380. 15p. - Publication Year :
- 2018
-
Abstract
- <bold>Background and Aims: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>The results suggested that Nrf2 suppressed intestinal fibrosis by inhibiting ROS/TGF-β1/SMADs pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]
- Subjects :
- *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
Subjects
Details
- Language :
- English
- ISSN :
- 01632116
- Volume :
- 63
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Digestive Diseases & Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 127794553
- Full Text :
- https://doi.org/10.1007/s10620-017-4710-z