title: The Protective Roles of IL-6 Trans-Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride-Induced Liver Injury in Mice.
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.
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China. sanqiangli2001@163.com.
authors.forename: San-Qiang
authors.initials: SQ
authors.lastname: Li
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
authors.affiliation: Department of Microbiology Immunology, College of Basic Medical Sciences, Zhengzhou University, 45001, People's Republic of China.
authors.forename: Sha
authors.initials: S
authors.lastname: Zhu
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Meng
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Han
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Hua-Jie
authors.initials: HJ
authors.lastname: Lu
mesh_terms: D051722:ADAM Proteins / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D008565:Membrane Proteins; D020011:Protective Agents; D002251:Carbon Tetrachloride; D051722:ADAM Proteins; C498316:Adam9 protein, mouse
keywords: ADAM9; CCl4; IL-6 Trans-Signaling