下调和上调
促炎细胞因子
胆固醇7α羟化酶
CYP8B1
胆汁酸
肝细胞
蛋白质组学
生物
化学
免疫系统
胆汁淤积
肝损伤
氧化应激
细胞生物学
细胞因子
酶
细胞
基因表达调控
免疫学
微阵列分析技术
肝细胞核因子
肝细胞
癌症研究
作者
Xinlei Liu,R. X. Liu,M Zhang,Di Ma,Yingming Tian,Yancheng Wang
标识
DOI:10.1021/acs.jproteome.5c00646
摘要
Concanavalin-A (ConA)-induced acute liver injury (ALI) is a widely used model for immune-mediated liver damage, but its molecular mechanisms remain poorly understood. We applied a multiomics approach that integrates transcriptomics, metabolomics, and proteomics to characterize the pathogenic features of ConA-induced ALI. Our analysis revealed significant downregulation of Cyp7a1 and Cyp8b1, two key enzymes in bile acid biosynthesis, as potential hallmark features of this model. Mechanically, suppression of these genes was correlated with altered bile acid metabolism, increased proinflammatory cytokine production (e.g., TNF-α, IL-6, and IL-1β), and elevated markers of hepatocyte apoptosis. Furthermore, multiomics network analysis highlighted interactions among bile acid dysregulation, oxidative stress, and immune activation, suggesting a synergistic role in ConA-induced liver injury. These findings improve our understanding of immune-mediated ALI and suggest the downregulation of Cyp7a1/Cyp8b1 as a diagnostic marker or therapeutic target for acute hepatotoxicity.
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