非酒精性脂肪性肝炎(NASH)是严重威胁人类健康的一种慢性肝病，其复杂病理过程受多种因素调控，其中炎症被认为是NASH的主要驱动力。泛素化通过改变蛋白定位、活性和降解等功能，参与免疫和炎症相关信号通路调控，阐明炎症通路的泛素化修饰调控机理对预防和治疗NASH具有重要意义。单核细胞趋化蛋白-1诱导蛋白1（Mcpip1）具有去泛素化活性，是重要的免疫炎症抑制因子，但Mcpip1在NASH中的作用及机制尚无报道。本项目前期初步研究显示，Mcpip1在NASH模型小鼠的肝脏组织和肝细胞中低表达，并对高脂饮食诱导的NASH具有抑制作用，且该抑制作用可能由泛素化途径介导。后期拟利用Mcpip1去泛素化活性突变体的相关工具病毒，感染细胞和动物模型，结合互作质谱与定量泛素化蛋白组学分析，深入探讨Mcpip1去泛素化活性调控NASH的具体分子机制，为寻求NASH治疗策略提供理论依据和潜在靶点。

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease, which is a serious threat to human health. Its complex pathological process is regulated by many factors, among which inflammation is considered to be the main driving force of NASH. Ubiquitination is involved in the regulation of immune and inflammation related signaling pathways by changing the functions of protein location, activity and degradation. It is of great significance to elucidate the mechanism of ubiquitination modification and regulation of inflammatory pathways for the prevention and treatment of NASH. Monocyte chemoattractant protein-1-inducible protein-1 (Mcpip1) is an important immunosuppressive factor with de-ubiquitination activity, but the role and mechanism of Mcpip1 in NASH have not been reported. The preliminary study of this project showed that Mcpip1 was low expression in the liver tissue and hepatocytes of NASH model mice, and had an inhibitory effect on NASH induced by high-fat diet, which might be mediated by ubiquitination pathway. In the later stage, we intend to use the related tool viruse which loaded Mcpip1 de-ubiquitination activity mutants, to infect cells and animal models, combined with interaction mass spectrometry and quantitative ubiquitination proteomics analysis, to further explore the specific molecular mechanism of Mcpip1 de-ubiquitination activity regulating NASH, so as to provide theoretical basis and potential targets for NASH treatment.