Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver
Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver
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DOI：
10.1093/emboj/21.7.1782
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发表时间：
2002-04-02
期刊：
影响因子：
11.4
通讯作者：
Wagner, EF
中科院分区：
文献类型：
--
作者：
Behrens, A;Sibilia, M;Wagner, EF
缺乏AP-1转录因子c-jun的小鼠在妊娠中期死亡，表现出心脏缺陷和肝细胞受损。为了使c-jun在肝细胞中失活，产生携带floxed c-jun等位基因的小鼠。围产期肝脏特异性c-jun缺失导致肝细胞增殖减少和体型缩小。部分肝切除后，一半的突变体死亡，肝再生受损。这种表型不存在于缺乏c-Jun的N-末端磷酸化位点的小鼠中。再生失败伴随着肝细胞中细胞死亡和脂质积累的增加。此外，细胞周期蛋白依赖性激酶和几种细胞周期调节因子受到影响，导致G（1）-S期进展效率低下。这些研究确定c-Jun是肝脏发育和再生过程中肝细胞增殖和存活的关键调节因子。
Mice lacking the AP-1 transcription factor c-jun die at mid-gestation showing heart defects and impaired hepatogenests. To inactivate c-jun in hepatocytes, mice carrying a floxed c-jun allele were generated. Perinatal liver-specific c-jun deletion caused reduced hepatocyte proliferation and decreased body size. After partial hepatectomy, half of the mutants died and liver regeneration was impaired. This phenotype was not present in mice lacking the N-terminal phosphorylation sites of c-Jun. The failure to regenerate was accompanied by increased cell death and lipid accumulation in hepatocytes. Moreover, cyclin-dependent kinases and several cell cycle regulators were affected, resulting in inefficient G(1)-S phase progression. These studies identify c-Jun as a critical regulator of hepatocyte proliferation and survival during liver development and regeneration.