Adenovirus-mediated gene expression in the septal cells of cirrhotic rat livers
Section snippets
Animals
Thirty male Wistar rats weighing 150 g were purchased from Shizuoka Laboratory Animal Center (Japan). Liver cirrhosis was induced by intraperitoneal injection with 1 ml of CCl4: olive oil (1:1 mixture) per kg of body weight, twice a week for 4–8 weeks, as described previously 12., 13.. These rats were classified into fibrotic and cirrhotic groups by liver-specific enzyme activities in sera, and by histological features of the livers. Asparate aminotransferase (AST) and alanine aminotransferase
Induction of cirrhosis by treatment with CCl4
Adenovirus vectors are well known to transfer a gene effectively to hepatocytes through blood circulation. Liver cirrhosis is characterized by the formation of fibrous septa following hepatic necrosis and fibrosis. Therefore, we questioned whether adenovirus vectors infect septal cells in the cirrhotic liver. To prepare the animal model for fibrosis and cirrhosis, CCl4 was administered to Wistar rats twice a week for 4–8 weeks. Progression of cirrhosis was monitored by AST and ALT activities in
Discussion
Adenovirus vectors are an efficient tool for a gene delivery system to the liver in vivo. These vectors are able to carry a comparatively large segment of DNA (up to 7 kb) (17), and can be prepared in high density (18). Furthermore, the adenovirus infects non-replicating cells as well as replicating cells. Because of their extremely high infectivity, adenovirus vectors are frequently used for gene transfer into hepatocytes through the blood circulation from the portal vein, abdominal cavity or
Acknowledgements
We are grateful to Dr. E. Nanba, Gene Research Center Tottori University for useful discussion in this study, and to Dr. J. Miyazaki for providing the CAG promoter.
Supported by grant no. 09670155 from the Japanese Ministry of Education.
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