title: Over-expression of uPA increases risk of liver injury in pAAV-HBV transfected mice.
abstract: OBJECTIVE
  To investigate the relationship between over-expression of urokinase plasminogen activator (uPA) and hepatitis B virus (HBV) related liver diseases in a transgenic mouse model.
  
  
  METHODS
  Albumin-tetracycline reverse transcriptional activator and tetO-uPA transgenic mice were generated respectively through pronuclear injection and crossed to produce the double transgenic in-alb-uPA mice, for which doxycycline (Dox)-inducible and liver-specific over-expression of uPA can be achieved. Hydrodynamic transfection of plasmid adeno-associated virus (AAV)-1.3 HBV was performed through the tail veins of the Dox-induced in-alb-uPA mice. Expression of uPA and HBV antigens were analyzed through double-staining immunohistochemical assay. Cytokine production was detected by enzyme linked immunosorbent assay and α-fetoprotein (AFP) mRNA level was evaluated through real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  Plasmid AAV-1.3 HBV hydrodynamic transfection in Dox-induced transgenic mice not only resulted in severe liver injury with hepatocarcinoma-like histological changes and hepatic AFP production, but also showed an increased serum level of HBV antigens and cytokines like interleukin-6 and tumor necrosis factor-α, compared with the control group.
  
  
  CONCLUSIONS
  Over-expression of uPA plays a synergistic role in the development of liver injury, inflammation and regeneration during acute HBV infection.
authors.affiliation: Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Shi-Hui
authors.initials: SH
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Jing-Ya
authors.initials: JY
authors.lastname: Hu
authors.forename: Shi-Cheng
authors.initials: SC
authors.lastname: Shang
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D000229:Dependovirus / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology; D006515:Hepatitis B virus / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012306:Risk; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology*; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: D016207:Cytokines; D000509:alpha-Fetoproteins; D004317:Doxorubicin; D014568:Urokinase-Type Plasminogen Activator