Stimulation of hepatocyte survival and suppression of CCl₄-induced liver injury by the adenovirally introduced C/EBP?? gene

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• 作者：Isoda ; Katsuhiro ; Koide ; Hiroko ; Kojima ; Midori ; Arita ; Eri ; Ikkaku ; Masahiro ; Higashiyama ; Shinji ; et. al.
• 关键词：C/EBP???? ; COX-2 ; Adenovirus ; Hepatocytes ; Gene therapy ; Liver injury
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：April 1, 2005
• 年：2005
• 卷：329
• 期：1
• 页码：182-187
• 全文大小：303 K

文摘

Gene therapy has attracted attention as a potentially effective alternative to liver transplantation for the treatment of hepatic failure. We chose the C/EBP?? gene, which plays vital roles in liver regeneration, as a candidate for gene therapy, and examined its effect on hepatocyte survival and the suppression of liver inflammation. C/EBP?? gene overexpression significantly maintained hepatocyte viability during 12 days of the culture. Urea synthesis ability, which is a liver-specific function, in Adv-C/EBP??-infected hepatocytes was stably maintained during the culture, but the activity per cell was significantly lower than that in non-infected cells. On the contrary, DNA synthesis activity in Adv-C/EBP??-infected hepatocytes was significantly higher than that in non-infected cells. COX-2 was induced in Adv-C/EBP??-infected hepatocytes, and the addition of NS398, a specific inhibitor of COX-2, suppressed the viability-maintenance effect. COX-2 was thus shown to be involved in the survival effect of C/EBP?? gene. The introduction of the C/EBP?? gene into liver-damaged mice significantly suppressed the serum AST and ALT activities. These results indicate that C/EBP?? appears to be a survival factor under stressful conditions, and the introduction of the gene has therapeutic function against liver injury.