title: Neutralization of ADAM8 ameliorates liver injury and accelerates liver repair in carbon tetrachloride-induced acute liver injury.
abstract: Although some studies have described the function of ADAM8 (a disintegrin and metalloprotease 8) related with rheumatoid arthritis, cancer and asthma, etc., the concrete role of ADAM8 in acute liver injury is still unknown. So mice respectively received anti-ADAM8 monoclonal antibody (mAb) of 100 μg/100 μl, 200 μg/100 μl or 300 μg/100 μl in PBS or PBS pre-injection. Then acute liver injury was induced in the mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl₄). Serum AST and ALT level, Haematoxylin-eosin (H&E) staining, the expression level of vascular endothelial growth factor (VEGF), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the mice after CCl4 administration. Our results showed that anti-ADAM8 mAb pre-injection could effectively lower AST and ALT levels (P < 0.05 or P < 0.01) and reduce liver injury (P < 0.05 or P <0.01), induce the expression of VEGF, CYP1A2 and PCNA (P <0.05 or P < 0.01) in dose-dependent manner compared with the control mice which received PBS pre-injection. In summary, our study suggested that ADAM8 might promote liver injury by inhibiting the proliferation of hepatocytes, angiogenesis and affecting the metabolism function of liver during acute liver injury induced by CCl₄. Anti-ADAM8 mAb injection might be suitable as a potential method for acute liver injury therapy.
authors.affiliation: The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, China.
authors.forename: San-Qiang
authors.initials: SQ
authors.lastname: Li
authors.forename: Sha
authors.initials: S
authors.lastname: Zhu
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Wan
authors.forename: Zheng-Shun
authors.initials: ZS
authors.lastname: Xu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Ma
mesh_terms: D051722:ADAM Proteins / Q000276:immunology* / Q000502:physiology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity*; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019388:Cytochrome P-450 CYP1A2 / Q000097:blood; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D007274:Injections, Intraperitoneal; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D002251:Carbon Tetrachloride; D019388:Cytochrome P-450 CYP1A2; D000410:Alanine Transaminase; D051722:ADAM Proteins; C489402:Adam8 protein, mouse