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首页> 外文期刊>American Journal of Physiology >Nrf2 is essential for timely M phase entry of replicating hepatocytes during liver regeneration
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Nrf2 is essential for timely M phase entry of replicating hepatocytes during liver regeneration

机译：NRF2对于在肝脏再生期间及时的M相入口是复制肝细胞的必要条件

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The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates various cellular activities, including redox balance, detoxification, metabolism, au-tophagy, proliferation, and apoptosis. Several studies have demonstrated that Nrf2 regulates hepatocyte proliferation during liver regeneration. The aim of this study was to investigate how Nrf2 modulates the cell cycle of replicating hepatocytes in regenerating livers. Wild-type and Nrf2 null mice were subjected to 2/3 partial hepatectomy (PH) and killed at multiple time points for various analyses. Nrf2 null mice exhibited delayed liver regrowth, although the lost liver mass was eventually restored 7 days after PH. Nrf2 deficiency did not affect the number of hepatocytes entering the cell cycle but did delay hepatocyte mitosis. Mechanistically, the lack of Nrf2 resulted in increased mRNA and protein levels of hepatic cyclin A2 when the remaining hepatocytes were replicating in response to PH. Moreover, Nrf2 deficiency in regenerating livers caused dysregulation of Wee 1, Cdc2, and cyclin Bl mRNA and protein expression, leading to decreased Cdc2 activity. Thus, Nrf2 is required for timely M phase entry of replicating hepatocytes by ensuring proper regulation of cyclin A2 and the Weel/Cdc2/cyclin Bl pathway during liver regeneration.
机译：转录因子核因子红细胞2相关因子2（NRF2）调节各种细胞活性，包括氧化还原平衡，排毒，代谢，Au-Tophagy，增殖和凋亡。几项研究表明，NRF2调节肝脏再生期间的肝细胞增殖。本研究的目的是研究NRF2如何调节在再生肝脏中复制肝细胞的细胞周期。对野生型和NRF2含氟小鼠进行2/3部分肝切除术（pH）并在多个时间点杀死各种分析。 NRF2含氟小鼠表现出延迟肝脏再生，尽管肝脏损失最终在pH后7天后恢复。 NRF2缺乏不影响进入细胞周期的肝细胞的数量，但延迟肝细胞有丝分裂。机械地，当剩余的肝细胞响应pH复制时，缺乏NRF2导致肝细胞周期蛋白A2的mRNA和蛋白质水平增加。此外，再生肝脏的NRF2缺乏引起了WEE1，CDC2和Cyclin BL mRNA和蛋白质表达的缺陷，导致CDC2活性降低。因此，通过确保在肝脏再生期间的适当调节细胞周期蛋白A2和Weel / CDC2 / Cyclin BL途径来及时M相进入时及时M相入物。

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