The Protective Roles of IL‐6 Trans‐Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride‐Induced Liver Injury in Mice |
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| Authors: | San‐Qiang Li Dong‐Mei Wang Sha Zhu Hong‐Ye Meng Hong‐Mei Han Hua‐Jie Lu |
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| Affiliation: | 1. The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China;2. Department of Microbiology Immunology, College of Basic Medical Sciences, Zhengzhou University, People's Republic of China |
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| Abstract: | Our study was undertaken to evaluate the important role that a disintegrin and metalloproteinase 9 (ADAM9) regulates IL‐6 trans‐signaling in carbon tetrachloride (CCl4)‐induced liver injury in mice. Mice were divided into four groups. Each group respectively received mineral oil injection, CCl4 injection, anti‐ADAM9 monoclonal antibody (mAb) pretreatment and CCl4 injection, anti‐ADAM9 mAb and recombinant mouse ADAM9 molecules pretreatment with CCl4 injection. Our results showed that anti‐ADAM9 mAb pretreatment significantly aggravated liver injury, inhibited IL‐6 trans‐signaling, which led to downregulation of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), upregulation of Caspase3, cytochrome P450 2E1 (CYP2E1), and hepatocytes apoptosis at 24 h after CCl4 injection. Recombinant ADAM9 molecules pretreatment reversed the impact of anti‐ADAM9 mAb pretreatment in mice. In conclusion, our study suggested that ADAM9 could regulate the hepatocytes proliferation, apoptosis, angiogenesis, and CYP2E1 expression by activating IL‐6 trans‐signaling and play important protective roles during CCl4‐induced liver injury in mice. |
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| Keywords: | IL‐6 Trans‐Signaling ADAM9 CCl4 |
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