ABRO1是重要的泛素调节蛋白，其在肝损伤中的作用未见报道。我们前期的研究发现：1）ABRO1-/-小鼠抵抗LPS/D-Gal诱导的急性肝衰竭，表现为提高存活率、减轻肝损伤、降低细胞因子水平、减少炎症细胞侵入等；2）ABRO1-/-小鼠的抵抗能力依赖血液来源细胞，与肝实质细胞关系不大；3）LPS体外刺激ABRO1-/- kupffer细胞产生TNF-α减少；4）ABRO1-/-成纤维细胞TNFα-NFκB信号通路活化受阻。因此，我们推测，敲除ABRO1可能通过抑制kupffer细胞TLR4-NFκB信号通路活化来保护LPS/D-Gal诱导的急性肝衰竭。本项目拟重点开展以下研究：1）ABRO1调控kupffer细胞炎性活化；2）鉴定ABRO1调控LPS/TLR4-NFκB通路的靶分子；3）ABRO1调控靶分子的机制；4）ABRO1/BRCC3作为抗肝脏炎症靶点的初步验证。

ABRO1 plays a pivotal role in the regulation of ubiquitination, but its function in liver injury is still unclear.Previous studies in our lab showed that: 1) ABRO1 -/- mice were resistance to LPS/D-Gal induced acute hepatic failure, showed higher survival rate, less severe liver injury, lower level of serum cytokines and fewer inflammatory cells invaded in liver. 2) That ABRO1 deficiency protects LPS/D-Gal induced acute hepatic failure was dependent on the hematopoietic cells. 3) Significant Less TNFα was detected in ABRO1-/- kupffer cells treated with LPS. 4) TNFα-NFκB signaling pathway was suppressed in ABRO1-/- MEF cells. Accordingly, we presumed that ABRO1 deficiency protects LPS/D-Gal induced acute hepatic failure in mice via suppressed TLR4 signaling pathway in kupffer cells. Therefore, We intend to focus on the following aspects: 1) The regulation of ABRO1 in the inflammatory activation of kupffer cells. 2) The molecular targets of ABRO1 in LPS/TLR4-NKkB pathay. 3) The mechanisms of ABRO1 in the regulation of it’s targets. 4) Preliminary study to confirm that ABRO1/BRCC3 can perform as a target for the treatment of hepatitis.