The Protective Roles of IL-6 Trans-Signaling Regulated by ADAM9 on the Liver in Carbon Tetrachloride-Induced Liver Injury in Mice

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 inje...

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Published inJournal of biochemical and molecular toxicology Vol. 29; no. 7; pp. 340 - 348
Main Authors Li, San-Qiang, Wang, Dong-Mei, Zhu, Sha, Meng, Hong-Ye, Han, Hong-Mei, Lu, Hua-Jie
Format Journal Article
LanguageEnglish
Published United States Blackwell Publishing Ltd 01.07.2015
Wiley Subscription Services, Inc
Subjects
ADAM Proteins - pharmacology
ADAM Proteins - physiology
ADAM9
Animals
Apoptosis - drug effects
Carbon Tetrachloride - toxicity
CCl4
Cell Proliferation - drug effects
IL-6 Trans-Signaling
Interleukin-6 - pharmacology
Liver - drug effects
Liver - metabolism
Male
Membrane Proteins - pharmacology
Membrane Proteins - physiology
Mice
Protective Agents - pharmacology
Signal Transduction
ADAM9
CCl4
IL-6 Trans-Signaling
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Summary: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.
Bibliography:National Natural Science Foundation of China - No. U1204802
Henan Province's Key Project of Tackle Key Problems of Science and Technology - No. 122102310030
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istex:2E4C258680EF8D3374D0E9E71C7594298DCCD44B
ArticleID:JBT21714
Science & Technology Innovation Talents in Universities of Henan Province - No. 13HASTIT025
Contract Grant Number: 122102310030
Contract Grant Sponsor: Henan Province's Key Project of Tackle Key Problems of Science and Technology
Contract Grant Number: U1204802
Contract Grant Number: 13HASTIT025
Contract Grant Sponsor: Science & Technology Innovation Talents in Universities of Henan Province
Contract Grant Sponsor: National Natural Science Foundation of China
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.21714