Can Nrf2 Modulate the Development of Intestinal Fibrosis and Cancer in Inflammatory Bowel Disease?

Abstract

One of the main mechanisms carried out by the cells to counteract several forms of stress is the activation of the nuclear factor erythroid 2-related factor (Nrf2) signaling. Nrf2 signaling controls the expression of many genes through the binding of a specific cis-acting element known as the antioxidant response element (ARE). Activation of Nrf2/ARE signaling can mitigate several pathologic mechanisms associated with an autoimmune response, digestive and metabolic disorders, as well as respiratory, cardiovascular, and neurodegenerative diseases. Indeed, several studies have demonstrated that Nrf2 pathway plays a key role in inflammation and in cancer development in many organs, including the intestine. Nrf2 appears to be involved in inflammatory bowel disease (IBD), an immune-mediated chronic and disabling disease, with a high risk of developing intestinal fibrotic strictures and cancer. Currently, drugs able to increase cytoprotective Nrf2 function are in clinical trials or already being used in clinical practice to reduce the progression of some degenerative conditions. The role of Nrf2 in cancer development and progression is controversial, and drugs able to inhibit abnormal levels of Nrf2 are also under investigation. The goal of this review is to analyze and discuss Nrf2-dependent signals in the initiation and progression of intestinal fibrosis and cancers occurring in IBD.

Real-Ambient Particulate Matter Exposure-Induced Cardiotoxicity in C57/B6 Mice

“…Nrf2 is one of the antioxidant genes that received high level of attentions. While Nrf2-mediated cardiac protection has commonly been reported in various studies (Deng et al, 2013;Smith et al, 2016;Erkens et al, 2018), the mixed roles of Nrf2 in various pathogenesis process and inflammation have also been reported (Satta et al, 2017;da Costa et al, 2019;Pompili et al, 2019). Specifically, negative effects of Nrf2 in cardiovascular diseases were reported (Barajas et al, 2011;Harada et al, 2012).…”

The Charming World of the Extracellular Matrix: A Dynamic and Protective Network of the Intestinal Wall

“…The ECM does not represent a static structure, but a dynamic tissue component that constantly undergoes continuous remodeling (10,11,18,22,62). The homeostasis of healthy tissue is guaranteed by a continuous and balanced deposition, degradation, and modification of the ECM and an imbalance in this equilibrium can lead to pathological conditions (63)(64)(65). A large number of molecules and growth factors orchestrate this delicate process by regulating ECM amount, composition, and structure (10,11,18,62).…”

Dimethyl fumarate protects nucleus pulposus cells from inflammation and oxidative stress and delays the intervertebral disc degeneration

“…The degenerative disease of the intervertebral disc also has an inflammatory reaction accompanied by the pathological increase of oxygen radicals in the body ( 41 ). The role of Nrf2 in antioxidation and anti-inflammation has been recognized in a number of diseases, such as myocardial infarction and inflammatory bowel disease ( 42 , 43 ); however, and whether these functions of Nrf2 are also closely associated with degenerative diseases of intervertebral disc is unclear. The PI3K/Akt pathway regulates apoptosis during oxidative stress.…”