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AIM:To investigate the relationship between overexpression 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)1.3HBV 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-1.3HBV 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.CONCLUSION:Over-expression of uPA plays a synergistic role in the development of liver injury,inflammation and regeneration during acute HBV infection.
AIM: To investigate the relationship between overexpression 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 performed respectively 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 achieved. Hydrodynamic transfection of plasmid adeno-associated virus (AAV) 1.3 HBV was Perform 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 alpha-fetoprotein (AFP) mRNA level was evaluated via real-time quantitative polymerase chain reaction .RESULTS: Plasmid AAV-1.3HBV hydrodynamic transfection in Dox-induced transgenic mice not only resulte d 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 .CONCLUSION: Over-expression of uPA plays a synergistic role in the development of liver injury, inflammation and regeneration during acute HBV infection.