Abstract
Nrf2 (NF-E2-related factor 2) is a master regulator of cellular oxidative levels against environmental stresses. Nrf2 induces the expression of metabolic detoxification and antioxidant enzymes to eliminate reactive oxygen species (ROS). The gastrointestinal tract is a key source of ROS. Intestinal barrier is critical to maintain the healthy steady state of the human gastrointestinal tract. Nrf2 has been shown to play important roles in maintaining the integrity of intestinal mucosal barrier. Here, we made a systematic review on the roles of Nrf2 in maintaining intestinal barrier, including the following: (1) NRF2 reduced intestinal mucosal injury by suppressing oxidative stress; (2) NRF2 decreased intestinal inflammation by inhibiting the inflammatory pathway; (3) NRF2 affected intestinal tight junction proteins and apoptosis of cells to regulate intestinal permeability; (4) NRF2 affected T cell differentiation and functions; (5) the crossregulation between the KEAP1-NRF2 pathway and autophagy controlled intestinal oxidative stress.
Highlights
The intestinal environment of the human body is very complex
We introduce that Keap1 dissociated from Nrf2 suppresses the ubiquitination and degradation of IκB, inhibiting the activation of NF-κB
It is crucial to understand the mechanism of intestinal barriers for the development and treatment of intestinal disease
Summary
The intestinal environment of the human body is very complex. Intestinal barrier plays a very important role in resisting the external environmental stress. The intestinal mucosa consists of several elements to form the physical and immunological defense barrier These elements mainly include the outer mucus layer with the intestinal commensal bacteria, antimicrobial peptides (AMPs), and secretory immunoglobulin A (sIgA) molecules, the central single cell layer with specialized epithelial cells, and the inner lamina propria which contains innate and adaptive immune cells such as T cells, B cells, macrophages, and dendritic cells [1]. Recent studies have found that the Nrf2-Keap pathway participates in many other cellular protective mechanisms besides countering oxidative stress, including the regulation of inflammatory pathways and tight junction (TJ) proteins in intestinal barrier. We will summarize the roles of the Nrf2-keap pathway in maintaining intestinal barrier through regulating oxidative stress, intestinal inflammation, intestinal permeability, and T cell activation and autophagy
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