Ni Yangyue, Huang Mengwen, Chen Shiyang, Wang Shihui, Chen Jianfeng
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Sep 14;56(11):1573-1583. doi: 10.3724/abbs.2024149.
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and poses a substantial health burden with increasing incidence globally. NAFLD encompasses a spectrum extending from hepatic steatosis to nonalcoholic steatohepatitis (NASH), with the possibility of progressing to cirrhosis or, in severe instances, hepatocellular carcinoma (HCC). NAFLD extends beyond simple metabolic disruption and involves multiple immune cell-mediated inflammatory processes. Integrins are a family of heterodimeric transmembrane cell adhesion receptors that regulate various aspects of NAFLD onset and progression, including hepatocellular steatosis, hepatic stellate cell (HSC) activation and immune cell infiltration. In this review, we comprehensively summarize the involvement of integrins in NAFLD, as well as the downstream signal transduction mediated by these receptors. Furthermore, we present the latest clinical and preclinical findings on drugs that target integrins for steatosis, inflammation, fibrosis and NAFLD-related HCC treatment.
非酒精性脂肪性肝病(NAFLD)是慢性肝病的主要病因,随着全球发病率的上升,它带来了沉重的健康负担。NAFLD涵盖了从肝脂肪变性到非酒精性脂肪性肝炎(NASH)的一系列病症,有可能发展为肝硬化,在严重情况下甚至会发展为肝细胞癌(HCC)。NAFLD不仅仅是简单的代谢紊乱,还涉及多种免疫细胞介导的炎症过程。整合素是一类异二聚体跨膜细胞粘附受体家族,它们调节NAFLD发生和发展的各个方面,包括肝细胞脂肪变性、肝星状细胞(HSC)激活和免疫细胞浸润。在这篇综述中,我们全面总结了整合素在NAFLD中的作用,以及这些受体介导的下游信号转导。此外,我们还介绍了针对整合素治疗脂肪变性、炎症、纤维化和NAFLD相关HCC的药物的最新临床和临床前研究结果。
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