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

키워드

Crohn's diseaseInflammatory bowel diseaseMicroRNAMAINTENANCE TREATMENTADALIMUMABPROLIFERATIONINFLIXIMABMIGRATIONMICRORNASTHERAPIES
제목
Role of miR-338-3p and miR-378a-3p as regulators in Crohn's disease pathogenesis: Potential therapeutic implications in inflammatory bowel disease
저자
Kim, Ki-UkMoon, Jung MinLim, EunsuDan, Kang-BinSeo, JeongkukKim, KyuwonShin, Seung YongMin, HyeyoungChoi, Chang Hwan
DOI
10.1016/j.lfs.2026.124217
발행일
2026-03
유형
Article
저널명
Life Sciences
389