Mechanisms regulating intestinal barrier integrity and its pathological implications

Abstract

The gastrointestinal tract is a specialized organ in which dynamic interactions between host cells and the complex environment occur in addition to food digestion. Together with the chemical barrier of the mucosal layer and the cellular immune system, the epithelial cell layer performs a pivotal role as the first physical barrier against external factors and maintains a symbiotic relationship with commensal bacteria. The tight junction proteins, including occludin, claudins, and zonula occludens, are crucial for the maintenance of epithelial barrier integrity. To allow the transport of essential molecules and restrict harmful substances, the intracellular signaling transduction system and a number of extracellular stimuli such as cytokines, small GTPases, and post-translational modifications dynamically modulate the tight junction protein complexes. An imbalance in these regulations leads to compromised barrier integrity and is linked with pathological conditions. Despite the obscurity of the causal relationship, the loss of barrier integrity is considered to contribute to inflammatory bowel disease, obesity, and metabolic disorders. The elucidation of the role of diseases in barrier integrity and the underlying regulatory mechanisms have improved our understanding of the intestinal barrier to allow the development of novel and potent therapeutic approaches. A better understanding of how the cells that line the inside of the intestines allow nutrients in, while keeping harmful substances and pathogens out could lead to new therapies for inflammatory bowel disease, obesity, and other conditions. A team from South Korea led by Sung Ho Ryu from Pohang University of Science and Technology review the regulatory mechanisms that help maintain the intestinal epithelial barrier. They discuss the role of tight junction proteins in forming a seal between adjacent cells and the various signaling pathways that loosen or tighten these junctions to enable limited transport. Loss of barrier integrity because of genetics, gut microbes, auto-immunity, diet, or other factors is often implicated in disease, and restoring barrier function with drugs or probiotics could help ameliorate many health problems.

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Affiliated Institutions

• Pohang University of Science and Technology KR
• NovaCell Technology (South Korea) KR

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