对葡萄糖皮质激素的依赖性和昼夜肝脏转录组的独立性
Robert J Maidstone1,2,3, A Louise Hunter4,5, Mudassar Iqbal6
1NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
Npj biological timing and sleep
|February 5, 2026
概括
葡萄糖皮质体受体 (GR) 结合与节奏性肝脏基因表达有关. 然而,删除肝细胞中的GR揭示了它在大多数肝脏基因中在维持昼夜节律方面基本上是多余的.
科学领域:
- 时间生物学 时间生物学
- 肝病学 肝病学是一种肝病学.
- 分子内分泌学分子内分泌学
背景情况:
- 肝脏在基因表达和代谢活动中表现出显著的每日变化,由内部分子钟和系统因素驱动.
- 葡萄糖皮质激素,具有强烈的昼夜振荡的激素,被认为是通过葡萄糖皮质受体 (GR) 影响肝脏昼夜节律的系统因素.
研究的目的:
- 研究葡萄糖皮质体受体 (GR) 结合在肝脏基因表达的昼夜调节中的作用.
- 确定肝细胞中GR信号的必要性,以维持肝脏基因的节奏表达.
主要方法:
- 对节律性肝脏基因的调节元件 (促进剂和增强剂) 的时钟因子和GR结合的比较分析.
- 在具有或没有肝细胞特异性GR缺失的小鼠中,表达节律基因表达的概况.
- 在GR结合部位和在GR删除时表现出改变节律性的基因之间的相关性分析.
主要成果:
- 在促进体的GR结合与基因表达的增加和节律性更高的可能性相关.
- 肝细胞特异性GR删除对肝转录组的整体节律性影响很小.
- 一小部分基因在GR删除时表现出改变的节律性 (丢失或获得),那些与GR结合部位相关的基因失去了节律性.
结论:
- 虽然GR结合与肝脏中的节律基因表达有关,但在大多数肝脏基因的昼夜调节中,肝细胞中的GR信号不是必不可少的.
- 这些发现表明,GR在很大程度上是冗余的,无法将时间信息传递到节律性肝脏转录组,这挑战了以前的假设.
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