Redox Imbalance in Intestinal Fibrosis: Beware of the TGFβ-1, ROS, and Nrf2 Connection

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2017 Dec 24

PMID 29273848

Citations 31

Authors

Giovanni Latella

Affiliations

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Abstract

Intestinal fibrosis, a common complication of inflammatory bowel diseases, becomes clinically apparent in ~ 40% of patients with Crohn's disease and ~ 5% of those with ulcerative colitis. Fibrosis, a consequence of local chronic inflammation, is characterized by excessive deposition of extracellular matrix (ECM) proteins by activated myofibroblasts, which are modulated by pro-fibrotic and anti-fibrotic factors. Fibrosis depends on the balance between production and degradation of ECM proteins. Although the transforming growth factor (TGF)-β1/Smad pathway is the major driving force of fibrosis, several pro-fibrogenic and anti-fibrogenic endogenous factors appear to interact directly with this pathway such as reactive oxygen species (ROS) and nuclear factor-erythroid 2-related factor 2 (Nrf2), which are connected with TGF-β1 during fibrosis development in several organs, including the intestine. Nrf2 is a ubiquitous master transcription factor that upregulates the expression of antioxidant enzymes and cytoprotective proteins mediated by antioxidant response elements (AREs). Here, I describe and discuss the links among TGF-β1, ROS, and Nrf2-AREs in the pathogenesis of intestinal fibrosis.

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