近日,武汉大学李红良、折志刚和徐海波等研究人员合作发现,TNIP3过表达通过阻碍TAK1激活来抑制非酒精性脂肪性肝炎(NASH)。2020年4月7日,国际知名学术期刊《细胞—代谢》发表了这一成果。
Title: TNFAIP3 Interacting Protein 3 Overexpression Suppresses Nonalcoholic Steatohepatitis by Blocking TAK1 Activation
Author: Dan Liu, Peng Zhang, Junjie Zhou, Rufang Liao, Yan Che, Mao-Mao Gao, Jiaqi Sun, Jingjing Cai, Xu Cheng, Yongping Huang, Guopeng Chen, Hongyu Nie, Yan-Xiao Ji, Xiao-Jing Zhang, Zan Huang, Haibo Xu, Zhi-Gang She, Hongliang Li
Issue&Volume: 2020/04/07
Abstract: Nonalcoholic steatohepatitis (NASH) is an unmet clinical challenge due to the rapidincrease in its occurrence but the lack of approved drugs to treat it. Further unravelingof the molecular mechanisms underlying NASH may identify potential successful drugtargets for this condition. Here, we identified TNFAIP3 interacting protein 3 (TNIP3)as a novel inhibitor of NASH. Hepatocyte-specific TNIP3 transgenic overexpressionattenuates NASH in two dietary models in mice. Mechanistically, this inhibitory effectof TNIP3 is independent of its conventional role as an inhibitor of TNFAIP3. Rather,TNIP3 directly interacts with TAK1 and inhibits its ubiquitination and activationby the E3 ligase TRIM8 in hepatocytes in response to metabolic stress. Notably, adenovirus-mediatedTNIP3 expression in the liver substantially blocks NASH progression in mice. Theseresults suggest that TNIP3 may be a promising therapeutic target for NASH management.
DOI: 10.1016/j.cmet.2020.03.007
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30122-4
Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx
本期文章:《细胞—代谢》:Online/在线发表