The Protective Roles of IL-6 Trans-Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride-Induced Liver Injury in Mice
The Protective Roles of IL-6 Trans-Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride-Induced Liver Injury in Mice
复制标题
ADAM9 调控的 IL-6 反式信号转导对四氯化碳所致小鼠肝损伤的保护作用
DOI：
10.1002/jbt.21714
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发表时间：
2015-07-01
影响因子：
3.6
通讯作者：
Lu, Hua-Jie
中科院分区：
文献类型：
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作者：
Li, San-Qiang;Wang, Dong-Mei;Lu, Hua-Jie
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 24h 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.
