小柯机器人

空军军医大学窦科峰、王琳等研究人员合作发现，TRIM16通过促进磷酸化TAK1的降解来改善非酒精性脂肪性肝炎。这一研究成果于2021年6月18日在线发表在国际学术期刊《细胞—代谢》上。

研究人员表示，非酒精性脂肪性肝炎（NASH）相关的肝细胞癌和肝脏疾病已成为发达国家肝移植的主要原因。脂毒性通过引起内质网应激和破坏蛋白质稳态在NASH进展中起着核心作用。

为了确定减轻脂毒性有害后果的关键分子，研究人员进行了综合多组学分析，并将E3连接酶TRIM16（tripartite motif 16）确定为候选分子。研究人员发现小鼠NASH模型中的脂质积累和炎症因TRIM16过表达而减轻，但因耗尽而加剧。多组学分析表明，TRIM16通过减弱丝裂原活化蛋白激酶（MAPK）信号通路的激活来抑制NASH进展；具体而言，通过优先与磷酸化TAK1相互作用来促进其降解。总之，这些结果表明TRIM16是治疗NASH的候选治疗靶点。

附：英文原文

Title: Tripartite motif 16 ameliorates nonalcoholic steatohepatitis by promoting the degradation of phospho-TAK1

Author: Lin Wang, Xin Zhang, Zhi-Bin Lin, Pei-Jun Yang, Hao Xu, Juan-Li Duan, Bai Ruan, Ping Song, Jing-Jing Liu, Zhen-Sheng Yue, Zhi-Qiang Fang, Heng Hu, Zhen Liu, Xiao-Li Huang, Ling Yang, Song Tian, Kai-Shan Tao, Hua Han, Ke-Feng Dou

Issue&Volume: 2021-06-18

Abstract: Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and liver disordershave become the leading causes for the need of liver transplantation in developedcountries. Lipotoxicity plays a central role in NASH progression by causing endoplasmicreticulum stress and disrupting protein homeostasis. To identify key molecules thatmitigate the detrimental consequences of lipotoxicity, we performed integrative multiomicsanalysis and identified the E3 ligase tripartite motif 16 (TRIM16) as a candidatemolecule. In particular, we found that lipid accumulation and inflammation in a mouseNASH model is mitigated by TRIM16 overexpression but aggravated by its depletion.Multiomics analysis showed that TRIM16 suppressed NASH progression by attenuatingthe activation of the mitogen-activated protein kinase (MAPK) signaling pathway; specifically,by preferentially interacting with phospho-TAK1 to promote its degradation. Together,these results identify TRIM16 as a promising therapeutic target for the treatmentof NASH.

DOI: 10.1016/j.cmet.2021.05.019

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00270-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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