Abstract
In recent years, chronic liver injury has become a common disease that harms human health. Its clinical manifestations are hepatic steatosis and secondary chronic steatohepatitis, which can quickly transform into liver fibrosis and cirrhosis if not treated in time. Therefore, this study is aimed at searching for new therapeutic targets of chronic liver injury and clarifying the molecular mechanisms of the new targets involved in chronic liver injury. After aquaporin 9 was identified as a target by proteomics, Aqp9−/− mice were constructed using the CRISPR/Cas9 system. Biochemical and morphological tests were used to verify the effect of Aqp9 knockout on early chronic liver injury. Proteomics, molecular biology, and morphology experiments were used to screen and verify the effects of Aqp9 knockout on its downstream pathway. Through the above experiments, we demonstrated that aquaporin 9 could be used as an intervention target for antagonizing the development of early chronic liver injury and its gene knockout affected downstream inflammation, oxidative stress, apoptosis, and pyroptosis by alleviating hepatic lipotoxicity.
Highlights
Chronic liver injury (CLI) is a common disease that harms human health [1], which mainly includes alcoholic liver injury, nonalcoholic liver injury, chemical liver injury, drug liver injury, immune liver injury, and viral liver injury
To further study the pathogenesis of early CLI and identify new targets for intervention in early CLI, we focused our follow-up studies on glycerol channel protein aquaporin 9 (AQP9), which played an important role in lipid metabolism
Many methods can intervene in CLI, most are not effective in preventing the progression of chronic hepatitis to liver fibrosis and cirrhosis
Summary
Chronic liver injury (CLI) is a common disease that harms human health [1], which mainly includes alcoholic liver injury, nonalcoholic liver injury, chemical liver injury, drug liver injury, immune liver injury, and viral liver injury. Its pathogenic factors and pathogenesis are complex. When the human body is exposed to harmful substances such as CCl4 and alcohol, the liver is the most vulnerable organ [2]. The accumulation of free fatty acids (FFAs) and glycerol after pathogenic factor attack of hepatocytes may lead to excessive lipid accumulation and peroxidation [3], which can further induce chronic inflammation and lead to steatohepatitis [4]. Clarifying the pathogenesis of early CLI and identifying new intervention targets are critical
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