Over-expression of uPA increases risk of liver injury in pAAV-HBV transfected mice

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.