NFκB prevents apoptosis and liver dysfunction during liver regeneration
NFκB prevents apoptosis and liver dysfunction during liver regeneration
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DOI：
10.1172/jci483
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发表时间：
1998-02-15
影响因子：
15.9
通讯作者：
Brenner, DA
中科院分区：
文献类型：
--
作者：
Iimuro, Y;Nishiura, T;Brenner, DA
尽管在肝部分切除后的肝再生过程中诱导了核因子-kappaB结合活性，但这种诱导的生理结果尚不清楚。我们使用表达突变形式I kappa Bα的腺病毒载体，通过向肝脏传递核因子kappaB活性的超抑制因子，评估了核因子kappa B在肝脏再生中的作用。这种腺病毒(Ad5I Kappa B)几乎只在肝脏中表达，并在体内抑制培养细胞和肝脏中NP kappa B的DNA结合活性和转录活性。肝部分切除后，感染Ad5I kappa B而不是对照组的腺病毒(Ad5LacZ)导致大量细胞凋亡和肝细胞的TUNEL分析，此外，感染Ad5I kappa B而不是Ad5LacZ降低了肝部分切除后的有丝分裂指数，这两种现象增加了细胞凋亡和未能通过细胞周期进行，这两种现象与感染Ad5I kappa B而不是Ad5LacZ的动物的肝功能障碍有关，如血清胆红素和氨水平升高所证明的那样，因此，在肝部分切除后肝再生过程中诱导核因子kappa B似乎是防止细胞凋亡和允许正常细胞周期进展的必需事件。
Although NF kappa B binding activity is induced during liver regeneration after partial hepatectomy, the physiological consequence of this induction is unknown. We have assessed the role of NF kappa B during liver regeneration by delivering to the liver a superrepressor of NF kappa B activity using an adenoviral vector expressing a mutated form I kappa B alpha. This adenovirus (Ad5I kappa B) was almost exclusively expressed in the liver and inhibited NP kappa B DNA binding activity and transcriptional activity in cultured cells as well as in the liver in vivo. After partial hepatectomy, infection with Ad5I kappa B, but not a control adenovirus (Ad5LacZ), resulted in the induction of massive apoptosis and hepatocytes as demonstrated by histological staining and TUNEL analysis, in addition, infection with Ad5I kappa B but not Ad5LacZ decreased the mitotic index after partial hepatectomy, These two phenomena, increased apoptosis and failure to progress through the cell cycle, were associated with liver dysfunction in animals infected with the Ad5I kappa B but not Ad5LacZ, as demonstrated by elevated serum bilirubin and ammonia levels, Thus, the induction of NF kappa B during liver regeneration after partial hepatectomy appears to be a required event to prevent apoptosis and to allow for normal cell cycle progression.