Tripartite motif 38 alleviates the pathological process of NAFLD–NASH by promoting TAB2 degradation

• DOI: 10.1016/j.jlr.2023.100382
• Publication Date: 2023-04-26T16:33:05Z
• Authors: Xinxin Yao; Ruixiang Dong; Sha Hu; Zhen Liu; Jie Cui; Fengjiao Hu; Xu Cheng; Xiaoming Wang; Tengfei Ma; Song Tian; Xiao-Jing Zhang; Yufeng Hu; Lan Bai; Hongliang Li; Peng Zhang
• Keywords: Steatosis; Steatohepatitis; Liver disease

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. Trim38, as an important member of TRIM (tripartite motif-containing) family, was largely reported to be involved regulation innate immune inflammatory responses. However, functional roles TRIM38 NAFLD remain unknown. Here, expression first detected samples both mice model patients diagnosed with NAFLD. We found that downregulated tissues compared normal tissues. Genetic Trim38-KO vivo showed depletion deteriorated high-fat diet high fat cholesterol diet-induced hepatic steatosis inflammation fibrosis. In particular, we effects hepatocellular lipid accumulation induced by palmitic acid oleic were aggravated but mitigated overexpression vitro. Mechanically, RNA-Seq analysis demonstrated ameliorated nonalcoholic steatohepatitis progression attenuating activation MAPK signaling pathway. further interacted transforming growth factor-β-activated kinase 1 binding protein 2 promoted its degradation, thus inhibiting 1-MAPK signal cascades. summary, our study revealed could suppress steatosis, inflammatory, fibrosis via promoting degradation. a potential target for treatment.