Role of miR-338-3p and miR-378a-3p as regulators in Crohn's disease pathogenesis: Potential therapeutic implications in inflammatory bowel disease.

Abstract

AIMS: Epithelial cell-derived microRNAs (miRNAs) are increasingly recognized as contributors to inflammatory bowel disease (IBD) through altered epithelial permeability and inflammatory cytokine production. This prospective study compared epithelial miRNA expression in Crohn's disease (CD) patients and healthy controls, and investigated their immunoregulatory role in experimental IBD models MATERIALS AND METHODS: Terminal ileum samples were collected via ileocolonoscopy from healthy controls and CD patients (remission and active state). Small-RNA sequencing identified unique miRNA profiles, including miR-338-3p and miR-378a-3p, validated by qRT-PCR. In dextran sodium sulfate-induced colitis mice, mimics were administered, and disease severity, gene expression, and immune cell infiltration were assessed by clinical, histological, and molecular assays KEY FINDINGS: miR-338-3p/miR-378a-3p mimics reduced disease activity scores, attenuated colon shortening, and decreased Th17 cell infiltration in colonic tissues. Histological and immunohistochemical analyses confirmed improved tissue integrity and reduced macrophage/T-cell infiltration in the colon. Mechanistically, miR-338-3p targeted MACC1, while miR-378a-3p suppressed IL33, a proinflammatory cytokine linked to CD pathogenesis. SIGNIFICANCE: The results underscore the distinct features of miR-338-3p and miR-378a-3p in CD mucosa and suggest their therapeutic potential for modulating immune responses in CD.