Faculty, Staff and Student Publications
Language
English
Publication Date
10-22-2025
Journal
JCI Insight
DOI
10.1172/jci.insight.190466
PMID
40956617
PMCID
PMC12581662
PubMedCentral® Posted Date
9-16-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The intestinal mucosal epithelium forms a barrier between luminal contents and the body. MicroRNAs (miRNAs) regulate mucosal homeostasis by controlling inflammatory responses and structural integrity. Here, we discovered a protective role for miR147 in intestinal inflammation using a miR147tdTomato reporter mouse. miR147 was enriched in the intestines, with the highest expression in the colonic epithelial cells at the luminal surface, with prominent expression in differentiated enterocytes. Mice with general or intestinal epithelial deletion of miR147 showed increased intestinal inflammation and diminished mucosal healing during colitis. RNA sequencing of miR147-deficient cells showed dysregulated immune signaling, with upregulated proinflammatory cytokine pathways and reduced type I interferon responses and revealed Ndufa4 as a likely miR147 target. Ndufa4, a mitochondrial protein regulating energy metabolism and inflammation, was elevated at the crypt base, inversely correlating with miR147. Mice lacking the miR147 binding site in Ndufa4's 3'-UTR phenocopied miR147-deficient mice during colitis. Spatial and single-cell transcriptomic analyses in murine and human colons showed mutually exclusive miR147 and Ndufa4 expression, consistent with a regulatory relationship in epithelial differentiation and metabolism. These findings underscore miR147's role in intestinal homeostasis and mucosal healing, suggesting it as a therapeutic target for inflammatory bowel disease.
Keywords
Animals, MicroRNAs, Intestinal Mucosa, Mice, Humans, Colitis, Inflammation, Disease Models, Animal, Mice, Inbred C57BL, Colon, Male, Mice, Knockout, Wound Healing
Published Open-Access
yes
Recommended Citation
Czopik, Agnieszka K; Dabiri, Arash; Tung, Chia-Hao; et al., "miR147 Promotes Mucosal Integrity and Healing in Intestinal Inflammation" (2025). Faculty, Staff and Student Publications. 755.
https://digitalcommons.library.tmc.edu/uthshis_docs/755