期刊
HEPATOLOGY RESEARCH
卷 43, 期 4, 页码 384-393出版社
WILEY
DOI: 10.1111/j.1872-034X.2012.01074.x
关键词
apoptosis; growth factor; heparin-binding epidermal growth factor-like growth factor; liver injury; Mx1-cre
资金
- Japan Society for the Promotion of Science
- Intractable Hepato-biliary Diseases Study Group in Japan (Health Labor Sciences Research Grant)
- Grants-in-Aid for Scientific Research [24570212, 23240126, 23590974] Funding Source: KAKEN
Aim: We previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is induced in response to several liver injuries. Because the HB-EGF knockout (KO) mice die in utero or immediately after birth due to cardiac defects, the loss of function study in vivo is limited. Here, we generated liver-specific HB-EGF conditional knockout mice using the interferon-inducible Mx-1 promoter driven cre recombinase transgene and investigated its role during acute liver injury. Methods: We induced acute liver injury by a single i.p. injection of carbon tetrachloride (CCl4) in HB-EGF KO mice and wild-type mice and liver damage was assessed by biochemical and immunohistochemical analysis. We also used AML12 mouse hepatocyte cell lines to examine the molecular mechanism of HB-EGF-dependent anti-apoptosis and wound-healing process of the liver in vitro. Results: HB-EGF KO mice exhibited a significant increase of alanine aminotransferase level and also showed a significant increase in the number of apoptotic hepatocytes assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining at 24h after CCl4 injection. We also demonstrated that HB-EGF treatment inhibited tumor necrosis factor--induced apoptosis of AML12 mouse hepatocytes and promoted the wound-healing response of these cells. Conclusion: This study showed that HB-EGF plays a protective role during acute liver injury.
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