The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier

Abstract

The gut is the body’s largest immune organ, and the intestinal barrier prevents harmful substances such as bacteria and toxins from passing through the gastrointestinal mucosa. Intestinal barrier dysfunction is closely associated with various diseases. However, there are currently no FDA-approved therapies targeting the intestinal epithelial barriers. Long noncoding RNAs (lncRNAs), a class of RNA transcripts with a length of more than 200 nucleotides and no coding capacity, are essential for the development and regulation of a variety of biological processes and diseases. lncRNAs are involved in the intestinal barrier function and homeostasis maintenance. This article reviews the emerging role of lncRNAs in the intestinal barrier and highlights the potential applications of lncRNAs in the treatment of various intestinal diseases by reviewing the literature on cells, animal models, and clinical patients. The aim is to explore potential lncRNAs involved in the intestinal barrier and provide new ideas for the diagnosis and treatment of intestinal barrier damage-associated diseases in the clinical setting.

Endoplasmic reticulum stress: A possible connection between intestinal inflammation and neurodegenerative disorders

“…To protect the intestinal mucosa from detrimental invasion of microorganisms, the intestinal epithelial cells produce a physical and chemical barrier. The first type of barrier includes: (i) the mucus layer, which coats the intestinal mucosa, (ii) the glycocalyx on the microvilli of absorptive intestinal epithelial cells, and (iii) the intracellular junctions (tight junctions, adherens junctions, and desmosomes) that firmly stabilize the mechanical cohesion of intestinal epithelial cells 36 …”

“…intracellular junctions (tight junctions, adherens junctions, and desmosomes) that firmly stabilize the mechanical cohesion of intestinal epithelial cells. 36 Claudin and occludin, transmembrane proteins, are the most important constituent of the tight junctions which forms a solid seal between the cells and representing a fundamental component of intestinal barrier. Recent studies of IBD development suggest that inflammation increases gut leakiness in part through alterations of claudin expression and localization 37 and that this leakiness promotes the probability that gut antigens will invade the submucosa, further exacerbate inflammation and pathology.…”

“…These barriers act in a concerted and cooperative manner and efficiently represent a spatial segregation to prevent unnecessary conflict between the microbiota and host immune cells, maintaining their symbiotic relationship in the intestine. 36 A second layer of protection to the invasion of microbes toward the intestinal mucosa is represented by the gut vascular barrier (GVB), lying in close proximity of the epithelial barrier. In physiological conditions the GVB is selectively permeable and blocks microbial dissemination into the portal and the systemic circulation.…”

“…The chemical barriers is formed by various antimicrobial peptides (AMPs) and the Reg3 family proteins, which are regulated by intestinal environmental factors and immune cell‐derived cytokines. These barriers act in a concerted and cooperative manner and efficiently represent a spatial segregation to prevent unnecessary conflict between the microbiota and host immune cells, maintaining their symbiotic relationship in the intestine 36 …”