miR-24 Is Elevated in Ulcerative Colitis Patients and Regulates Intestinal Epithelial Barrier Function

• Published in: The American journal of pathology Vol. 189; no. 9; pp. 1763 - 1774
• Main Authors: Soroosh, Artin, Rankin, Carl R., Polytarchou, Christos, Lokhandwala, Zulfiqar A., Patel, Ami, Chang, Lin, Pothoulakis, Charalabos, Iliopoulos, Dimitrios, Padua, David M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2019; American Society for Investigative Pathology
• Subjects: Apoptosis; Cell Membrane Permeability; Cell Proliferation; Colitis, Ulcerative - genetics; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Humans; Intestines - pathology; MicroRNAs - genetics; Tight Junctions - metabolism; Tight Junctions - pathology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2019.05.018

Inflammatory bowel disease is characterized by high levels of inflammation and loss of barrier integrity in the colon. The intestinal barrier is a dynamic network of proteins that encircle intestinal epithelial cells. miRNAs regulate protein-coding genes. In this study, miR-24 was found to be elevated in colonic biopsies and blood samples from ulcerative colitis (UC) patients compared with healthy controls. In the colon of UC patients, miR-24 is localized to intestinal epithelial cells, which prompted an investigation of intestinal epithelial barrier function. Two intestinal epithelial cell lines were used to study the effect of miR-24 overexpression on barrier integrity. Overexpression of miR-24 in both cell lines led to diminished transepithelial electrical resistance and increased dextran flux, suggesting an effect on barrier integrity. Overexpression of miR-24 did not induce apoptosis or affect cell proliferation, suggesting that the effect of miR-24 on barrier function was due to an effect on cell–cell junctions. Although the tight junctions in cells overexpressing miR-24 appeared normal, miR-24 overexpression led to a decrease in the tight junction–associated protein cingulin. Loss of cingulin compromised barrier formation; cingulin levels negatively correlated with disease severity in UC patients. Together, these data suggest that miR-24 is a significant regulator of intestinal barrier that may be important in the pathogenesis of UC.