MicroRNA-141’s Target Regulation And Therapy Research In IBD

Inflammatory Bowel Disease(IBD) is a chronic, autoimmune disease in Gastrointestinal tract.Abnormal immune caused by cytokine imbalance is the important pathogenesis of IBD. To investigate the regulation of cytokine is important for understanding the pathogenesis and the therapy of IBD. Recent studies have found that miRNA can regulate the immune system, but the miRNA regulatory mechanism of cytokines in IBD has not yet been clarified.In this paper we use TNBS-induced IBD mouse to establish mice miRNA expression profile of IBD by miRNA microarray technology and bioinformatics analysis; from the biological function of cytokines, we predicte chemokine CXCL12is the target of miR-141using TargetScan, Miranda and PicTarIn vitro, We used luciferase reporter system and find that miR-141can bind directly on the3’-UTR of CXCL12. We also isolated the primary colonic epitheliall cells and exmianed the mRNA and protein level of CXCL12β after the transfection of pre-miR-141. In vivo study we found that miRNA-141expression and CXCL12protein expression was negatively correlated in the colon tissue. These results suggest that miR-141play an important role in the pathogenesis of IBD by regulating chemokine CXCL12. On this basis, we apply the DAI score, HE and other methods to analysis miRNA-141as a therapeutic target for TNBS-induced IBD. The results fully demonstrate that miR-141can regulate the secretion of chemokine CXCL12, affect the recruitment of lymphocytes enteritis, and can effectively inhibit inflammation. This study provide new targets and new ideas for the treatment of inflammatory bowel disease...