| Popis: |
Background Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes among various liver surgery. However, there is still a lack of strategies against hepatic I/R injury because of the unrevealed inner mechanism. The present study aimed to identify a potential strategy for hepatic I/R injury and provide the fundamental experimental basis. Results Here we report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through reinforcement of IKK-induced inflammation following dual patterns. Mechanically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) thus igniting K63 ubiquitination, eventually leading to the phosphorylation of IKKβ. Meanwhile, TRIM37 enhances translocation of IKKγ, a regulatory subunit of IKK complex, from nucleus to cytoplasm thereby stabilizing cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK could rescue the function of TRIM37 both in vivo and in vitro. Conclusion Collectively, the present study discloses the critical role of TRIM37 facilitating hepatic I/R injury by activating IKK axis. Targeting TRIM37 might be potential for treatment against hepatic I/R injury. |
