Role of microRNA-449a in the progress of inflammatory bowel disease in children

Abstract

This study aimed to investigate the expression and role of microRNA-449a (miR-449a) in inflammatory bowel disease (IBD) in children, and further to explore the underlying mechanism. To study the role of miR-449a in IBD development, an in vitro inflammatory model of IBD was conducted by stimulating the normal intestinal epithelial cells Caco-2 with 2% dextran sulfate sodium (DSS). The results showed that the miR-449a level was significantly higher in children with IBD than that in children without IBD. Notch1 was a direct target gene of miR-449a. The increased levels of TNF-α, IL-1β and IL-6, reduced cell viability and enhanced cell apoptosis in Caco-2 cells caused by DSS administration were significantly inhibited by miR-449a inhibition. Besides, DSS significantly decreased the level of Notch1, Hes-1, Hey-1 and Bcl-2, and increased Bax expression, and these changes were prevented by miR-449a inhibitor. Importantly, all the effects of miR-449a inhibitor on Caco-2 cells were eliminated by Notch1 gene silencing. In conclusion, the data of our study indicated that miR-449a was up-regulated in IBD in children, and miR-449a inhibitor could inhibit inflammatory response and cell apoptosis by targeting Notch1 in IBD in vitro. The miR-449a/Notch1 axis might be a novel target for IBD treatment.