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

Abstract

Abstract 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.

Keywords

• colitis
• miR‐128‐3p
• NF‐κB
• rats
• TRAF6