MicroRNAs as Key Modulators of Intestinal Barrier Function: Pattern Recognition Receptors, Epithelial Junctional Complexes, and Therapeutic Approaches

PMID: 40544176
Source: Dig Dis Sci
Publication date: 2025-06-21
Year: 2025

Abstract

PURPOSE: This review aims to investigate the regulatory role of microRNAs (miRNAs) in intestinal barrier function, with a focus on their interaction with pattern recognition receptors (PRRs) such as Toll-like receptors (TLR2, TLR4, TLR5) and nucleotide-binding oligomerization domain (NOD) receptors. Additionally, the review explores how miRNAs influence epithelial junctional complexes-including tight junctions, adherens junctions, and desmosomes-and their implications in inflammatory bowel diseases (IBD). METHODS: A comprehensive literature review was conducted to examine recent studies focusing on miRNA-mediated modulation of signaling pathways related to PRRs and junctional complexes. Particular attention was given to the expression and regulation of key junctional complexes such as claudin, occludin, and zonula occludens, and their relationship with epithelial homeostasis. RESULTS: Emerging evidence demonstrates that miRNAs modulate both inflammatory signaling and structural junctional integrity. Dysregulated expression of specific miRNAs is associated with impaired barrier function and increased intestinal permeability, contributing to the pathogenesis of IBD. Moreover, experimental data suggest that miRNA mimics and antagomiRs may help restore epithelial barrier integrity and reduce inflammation. CONCLUSION: MiRNAs play a central role in maintaining intestinal barrier homeostasis by targeting PRRs and junctional complexes. Their ability to modulate inflammation and barrier function highlights their potential as therapeutic targets. miRNA-based strategies may offer novel, targeted treatments for IBD and other intestinal disorders.