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Integrins and NAFLD-associated liver diseases: clinical associations, pathophysiological mechanisms and
Yangyue Ni1,2, Mengwen Huang1,2, Shiyang Chen1
1Key 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.
Abstract:
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.
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