Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 28, 2012; 18(16): 1892-1902
Published online Apr 28, 2012. doi: 10.3748/wjg.v18.i16.1892
Over-expression of uPA increases risk of liver injury in pAAV-HBV transfected mice
Xiao-Jun Zhou, Shi-Hui Sun, Peng Wang, Hong Yu, Jing-Ya Hu, Shi-Cheng Shang, Yu-Sen Zhou
Xiao-Jun Zhou, Shi-Hui Sun, Hong Yu, Jing-Ya Hu, Yu-Sen Zhou, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
Peng Wang, Shi-Cheng Shang, Beijing Experimental Animal Center, Beijing 100071, China
Author contributions: Zhou XJ and Sun SH contributed equally to this work; all authors contributed to this work.
Supported by National Program of Infection Diseases, No. 2012ZX10004-502; The National High Technology Program (“863” Program) of China, No. 2007AA02Z151
Correspondence to: Dr. Shi-Hui Sun, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. shsun916@yahoo.com.cn
Telephone: +86-10-66948580 Fax: +86-10-66948580
Received: May 18, 2011
Revised: June 24, 2011
Accepted: April 1, 2012
Published online: April 28, 2012

AIM: 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)-1.3HBV 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.

Keywords: Tet-on system, Albumin promoter, Urokinase-type plasminogen activator, Hydrodynamic transfection, Liver injury