title: Adenovirus-mediated dual gene expression of human interleukin-10 and hepatic growth factor exerts protective effect against CCl4-induced hepatocyte injury in rats.
abstract: BACKGROUND
  Hepatocyte injury is a common pathological cause of various liver diseases. Due to a lack of an effective preventive treatment, gene therapy has become an interesting approach to prevent and alleviate liver injury.
  
  
  OBJECTIVE
  A protective effect of adenovirus-mediated dual gene expression of human interleukin-10 (hIL-10) and human hepatocyte growth factor (hHGF) was investigated against tetrachloromethane (CCl(4))-induced hepatocyte injury in rats.
  
  
  METHODS
  An adenoviral vector carrying the hIL-10 and hHGF genes was constructed, and its protective effect against rat hepatocyte injury was investigated both in vivo and in vitro.
  
  
  RESULTS
  In the in vitro CCl(4)-induced cell injury model, simultaneous transfection of hIL-10 and hHGF genes via an adenoviral vector resulted in production of anti-hepatocyte biological factors by an autocrine mechanism, then significantly improved hepatocyte viability. In the in vivo rat model, synergistic effects of these two gene products protected hepatocytes from damage by reducing the CC1(4)-induced hepatocyte degeneration, hepatic fibrosis, and intrahepatic inflammatory cell infiltration, thereby preserving liver function.
  
  
  CONCLUSIONS
  Adenovirus-mediated dual gene expression of hIL-10 and hHGF effectively protected against liver damage by likely regulating immune responses to reduce hepatocyte injury and by promoting hepatocyte regeneration. The hIL-10 and hHGF dual gene expression vector has significant potential in the field of liver disease therapeutics and constitutes one of the most promising current strategies for gene therapy.
authors.affiliation: Department of Biochemistry, Cancer Center of PLA, Nanjing 81 Hospital, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Jicheng
authors.initials: J
authors.lastname: Xing
authors.forename: Yuerong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lin
authors.initials: L
authors.lastname: Fang
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Cao
authors.forename: Changqing
authors.initials: C
authors.lastname: Su
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects* / Q000494:pharmacology; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D016753:Interleukin-10; D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride