细胞周期蛋白B1
肝再生
细胞生物学
生物
细胞周期
第1周
细胞周期蛋白
肝细胞
细胞周期蛋白E1
细胞周期蛋白
再生(生物学)
细胞周期蛋白D1
细胞周期蛋白依赖激酶1
有丝分裂
细胞周期蛋白B
细胞周期蛋白A2
细胞凋亡
生物化学
体外
作者
Yuhong Zou,Min Hu,Joonyong Lee,Shashank Manohar Nambiar,Veronica Garcia,Qi Bao,Jefferson Chan,Guoli Dai
出处
期刊:American Journal of Physiology-gastrointestinal and Liver Physiology
[American Physiological Society]
日期:2014-12-19
卷期号:308 (4): G262-G268
被引量:41
标识
DOI:10.1152/ajpgi.00332.2014
摘要
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates various cellular activities, including redox balance, detoxification, metabolism, autophagy, 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 Wee1, Cdc2, and cyclin B1 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 Wee1/Cdc2/cyclin B1 pathway during liver regeneration.
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