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

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. microRNAs regulate protein-coding genes. In this study, microRNA-24 was found to be elevated in colonic biopsies and blood samples from ulcerative colitis (UC) patients compared to healthy controls. In the colon of UC patients, microRNA-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 microRNA-24 in both cell lines led to diminished transepithelial electrical resistance and increased dextran flux, suggesting an effect on barrier integrity. Overexpression of microRNA-24 did not induce apoptosis or affect cell proliferation, suggesting that the effect of microRNA-24 on barrier function was due to an effect on cell-cell junctions. Although the tight junctions in cells overexpressing microRNA-24 appeared normal, microRNA-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 microRNA-24 is a significant regulator of intestinal barrier that may be important in the pathogenesis of UC.