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首页> 外文期刊>Cell cycle >Keap1 modulates the redox cycle and hepatocyte cell cycle in regenerating liver
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Keap1 modulates the redox cycle and hepatocyte cell cycle in regenerating liver

机译：Keap1调节再生肝脏中的氧化还原循环和肝细胞周期

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Keap1 negatively controls the activity of transcription factor Nrf2. This Keap1/Nrf2 pathway plays a critical role in combating oxidative stress. We aimed at determining whether and how Keap1 modulates the cell cycle of replicating hepatocytes during liver regeneration. Two-thirds partial hepatectomy (PH) was performed on wild-type mice and Keap1+/- (Keap1 knockdown) mice. We found that, following PH, Keap1 knockdown resulted in a delay in S-phase entry, disruption of S-phase progression, and loss of mitotic rhythm of replicating hepatocytes. These events are associated with dysregulation of c-Met, EGFR, Akt1, p70S6K, Cyclin A2, and Cyclin B1 in regenerating livers. Astonishingly, normal regenerating livers exhibited the redox fluctuation coupled with hepatocyte cell cycle progression, while keeping Nrf2 quiescent. Keap1 knockdown caused severe disruption in both the redox cycle and the cell cycle of replicating hepatocytes. Thus, we demonstrate that Keap1 is a potent regulator of hepatic redox cycle and hepatocyte cell cycle during liver regeneration.
机译：Keap1负控制转录因子Nrf2的活性。此Keap1 / Nrf2途径在抵抗氧化应激中起关键作用。我们旨在确定Keap1在肝再生过程中是否以及如何调节复制肝细胞的细胞周期。在野生型小鼠和Keap1 +/-（Keap1敲低）小鼠上进行了三分之二的肝部分切除术（PH）。我们发现，在PH之后，Keap1敲低导致S期进入的延迟，S期进程的破坏以及复制肝细胞的有丝分裂节律的丧失。这些事件与再生肝脏中c-Met，EGFR，Akt1，p70S6K，Cyclin A2和Cyclin B1的失调有关。令人惊讶的是，正常的再生肝脏在保持Nrf2静止的同时表现出氧化还原波动和肝细胞周期的变化。 Keap1敲低导致氧化还原周期和复制肝细胞的细胞周期严重破坏。因此，我们证明Keap1是肝脏再生过程中肝氧化还原周期和肝细胞周期的有效调节剂。

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