Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms

Abstract

The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders.

Clostridium Tyrobutyricum Protect Intestinal Barrier Function from LPS-Induced Apoptosis via P38/JNK Signaling Pathway in IPEC-J2 Cells

“…The intestinal epithelium, which represents the largest interface in the body, plays several important roles in the absorption of nutrients and prevention of water and electrolyte loss [21, 22]. In particular, the intestinal barrier can separate the internal milieu from the external environment via cell-cell adhesion and intercellular junctions that direct morphogenesis and maintain tissue integrity [2].…”

“…In particular, the intestinal barrier can separate the internal milieu from the external environment via cell-cell adhesion and intercellular junctions that direct morphogenesis and maintain tissue integrity [2]. Intestinal permeability is controlled by epithelial adherens junctions and TJs, with the increased intestinal permeability contributing to the severity of some diseases, such as inflammatory bowel disease and irritable bowel syndrome [21]. In the present study, an in vitro -simulated intestinal barrier was established by culturing IPEC-J2 cells in Transwells.…”

Vitamin D Receptor Deletion Leads to the Destruction of Tight and Adherens Junctions in Lungs

“…claudin-15), which were localized at the cell membrane of bronchial epithelium cells in VDR -/mice. Claudin-15 is a pore forming claudins, just like claudin-2 37 . The studies of claudin-15 are still limited.…”

Enhanced gut barrier integrity sensitizes colon cancer to immune therapy

“…It is well known that disruption of gut epithelial barrier can promote tumor growth via complex multi-pathway inflammatory processes that involve both microbial as well as non-microbial factors. 32,33 Specifically, both type 17 and type 1 T-cell activity, as well as innate inflammatory cells can contribute to tumor growth in the inflamed gut. 32,33 In the case of the APC min/+ / B fragilis model microbially-driven type 17 immunity has been shown to be essential to tumor development.…”

“…32,33 Specifically, both type 17 and type 1 T-cell activity, as well as innate inflammatory cells can contribute to tumor growth in the inflamed gut. 32,33 In the case of the APC min/+ / B fragilis model microbially-driven type 17 immunity has been shown to be essential to tumor development. 8,22,34 While our findings are consistent with this paradigm, the ability of IL-12 to exacerbate disease without significant impact on Th17 cells suggests that additional, yet unidentified, factors that are associated with increased gut permeability may also contribute to tumor pathogenesis in this model.…”