每日肝脏节奏:形态和分子振荡的结合
Ueli Schibler1, Flore Sinturel2, Felix Naef3
1Department of Molecular and Cellular Biology, Sciences III, Geneva CH-1205, Switzerland.
概括
肝脏
科学领域:
- 时间生物学
- 分子生物学
- 肝病学
背景情况:
- 哺乳动物生理是由一个等级的昼夜计时系统控制的,其中上神经核 (SCN) 作为主节拍器.
- 肝脏对于新陈代谢适应至关重要, 它表现出基因表达,蛋白质合成和排毒的日常节奏.
- 值得注意的是,肝脏质量和肝细胞形态在24小时内发生显著波动.
研究的目的:
- 调查肝脏质量和肝细胞大小日间波动的机制.
- 在调节这些昼夜节律方面探索actin细胞骨架和相关信号通路的作用.
- 了解这些细胞变化如何促进肝脏时钟的同步.
主要方法:
- 使用小鼠模型研究肝脏质量的每日波动,肝细胞大小,RNA和蛋白质积累.
- 分析了核糖体含量及其与蛋白质合成率的相关性.
- 通过肌肉激素相关的转录因子-血清反应因子 (MRTF-SRF) 信号调节的行为细胞骨动力学.
主要成果:
- 小鼠的肝脏质量每天波动30~40%,伴随着肝细胞大小和总蛋白质/RNA水平的节奏变化.
- 核糖体丰度与肝脏大小相关,作为白天蛋白质合成的速度限制因素.
- 肝细胞的行为细胞骨经历了显著的聚合周期,F-行为在夜间聚集,与最大的肝脏大小一致.
结论:
- 肝脏质量的循环节律是由肝细胞大小和核糖体含量的波动驱动的,影响蛋白质合成.
- 肝细胞中的阿克丁聚合周期对于保持细胞大小波动的稳健性至关重要.
- 受到actin动力学影响的MRTF-SRF信号传递,在像Per2这样的时钟基因的昼夜转录中发挥作用,同步肝脏时钟.
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