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The Protective Roles of IL‐6 Trans‐Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride‐Induced Liver Injury in Mice
Author(s) -
Li SanQiang,
Wang DongMei,
Zhu Sha,
Meng HongYe,
Han HongMei,
Lu HuaJie
Publication year - 2015
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21714
Subject(s) - proliferating cell nuclear antigen , ccl4 , liver injury , downregulation and upregulation , angiogenesis , chemistry , cyp2e1 , apoptosis , cancer research , signal transduction , microbiology and biotechnology , carbon tetrachloride , cell growth , pharmacology , biology , biochemistry , cytochrome p450 , enzyme , organic chemistry , gene
Our study was undertaken to evaluate the important role that a disintegrin and metalloproteinase 9 (ADAM9) regulates IL‐6 trans‐signaling in carbon tetrachloride (CCl 4 )‐induced liver injury in mice. Mice were divided into four groups. Each group respectively received mineral oil injection, CCl 4 injection, anti‐ADAM9 monoclonal antibody (mAb) pretreatment and CCl 4 injection, anti‐ADAM9 mAb and recombinant mouse ADAM9 molecules pretreatment with CCl 4 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 CCl 4 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 CCl 4 ‐induced liver injury in mice.