MiR-128-3p alleviates TNBS-induced colitis through inactivating TRAF6/NF-κB signaling pathway in rats.

miR-128-3p is reported to involve in pathogenesis of several autoimmune diseases, yet the role of miR-128-3p in inflammatory bowel disease (IBD) remains unknown. To investigate miR-128-3p in IBD, experimental colitis animal model was generated by 2,4,6-Trinitrobenzenesulfonic acid solution (TNBS). miR-128-3p agomir was used to overexpress miR-128-3p in rats. Histological assessment and myeloperoxidase activity were conducted to evaluate the TNBS-induced colitis. Effect of miR-128-3p overexpression on levels of TNF-α, IL-1β, ICAM-1, and MCP-1 was tested by ELISA assay. The target of miR-128-3p was predicted and further confirmed by dual-luciferase reporter assay. The expressions of TRAF6, p-NF-κB, and NF-κB were determined by western blot. The miR-128-3p level was significantly decreased in rats with TNBS-induced colitis. miR-128-3p could alleviate TNBS-induced colitis and inhibit production of inflammatory factors. We found TRAF6 was a direct target of miR-128-3p using bioinformatics and luciferase assay. By western blot, we discovered miR-128-3p activates NF-κB by targeting TRAF6. Our data reveal a novel mechanism that a decreased miR-128-3p level in TNBS-induced colitis could inhibit production of inflammatory factors, which activates NF-κB signaling by targeting TRAF6. Our findings might provide a novel therapeutic target for drug design and development for IBD therapeutics.