NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-ß1/SMADs Pathway.
Dig Dis Sci
; 63(2): 366-380, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-28815354
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-ß1 (TGF-ß1), 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-ß1/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-ß1/SMADs signaling pathway in TNBS-induced colitis and CCD-18Co cells. Moreover, Nrf2 knockdown enhanced the TGF-ß1-induced differentiation of CCD-18Co cells. ROS significantly increased in TGF-ß1-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-ß1. Moreover, scavenging ROS by N-acetyl cysteine could inhibit the increasing expression of TGF-ß1 promoted by Nrf2 knockdown.CONCLUSIONS:
The results suggested that Nrf2 suppressed intestinal fibrosis by inhibiting ROS/TGF-ß1/SMADs pathway in vivo and in vitro.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Fibrosis
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Especies Reactivas de Oxígeno
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Proteínas Smad
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Factor 2 Relacionado con NF-E2
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Factor de Crecimiento Transformador beta1
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Dig Dis Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
China