title: In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice: a comparative study to HGF.
abstract: OBJECTIVE
  It is unknown whether heparin-binding EGF-like growth factor (HB-EGF) can be a therapeutic agent, although previous studies suggested that HB-EGF might be a hepatotrophic factor. This study explores the potential of hepatic HB-EGF gene therapy in comparison with HGF.
  
  
  METHODS
  Mice received an intraperitoneal injection of the agonistic anti-Fas antibody 72 h after an intravenous injection of either adenoviral vector (1x10(11) particles) expressing human HB-EGF (Ad.HB-EGF), human HGF (Ad.HGF) or no gene (Ad.dE1.3), and were sacrificed 24 or 36 h later to assess liver injury and regeneration.
  
  
  RESULTS
  Exogenous HB-EGF was predominantly localized on the membrane, suggesting the initial synthesis of proHB-EGF in hepatocytes. The control Ad.dE1.3-treated mice represented remarkable increases in serum ALT and AST levels and histopathologically severe liver injuries with numerous apoptosis, but a limited number of mitogenic hepatocytes. In contrast, the liver injuries and apoptotic changes were significantly inhibited, but the mitogenic hepatocytes remarkably increased, in both the Ad.HB-EGF- and Ad.HGF-treated mice. More mitogenic hepatocytes and milder injuries were observed in the Ad.HB-EGF-treated mice.
  
  
  CONCLUSIONS
  HB-EGF has more potent protective and mitogenic effects for hepatocytes than HGF, at least for the present conditions. In vivo hepatic HB-EGF gene transduction is therapeutic for Fas-induced liver injury.
authors.affiliation: Department of Gene Therapy and Regenerative Medicine, Gifu University School of Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Ngin Cin
authors.initials: NC
authors.lastname: Khai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ushikoshi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagano
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yuge
authors.forename: Masayasu
authors.initials: M
authors.lastname: Esaki
authors.forename: Takao
authors.initials: T
authors.lastname: Kawai
authors.forename: Kazuko
authors.initials: K
authors.lastname: Goto
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Murofushi
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kosai
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000032:analysis / Q000235:genetics*; D015316:Genetic Therapy; D066257:Heparin-binding EGF-like Growth Factor; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000276:immunology / Q000628:therapy*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D019014:fas Receptor / Q000187:drug effects
chemical_list: D000906:Antibodies; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D019014:fas Receptor; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor