BMAL1的PAS-B域控制了人类单细胞细胞系THP-1中的增殖,细胞活力和炎症反应
Yoko Gozu1, Junichi Hosoi1, Hiroaki Nagatomo2
1Mirai Technology Institute, Shiseido Co., Ltd., Kanagawa 220-0011, Japan.
International journal of molecular sciences
|July 29, 2025
概括
BMAL1-PAS-B 域通过控制糖解来调节单细胞功能,如增殖和炎症. 抑制hexokinase 2模仿了这些效应,表明该域是治疗点.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 时间生物学 时间生物学
背景情况:
- 大脑肌肉ARNT-like1 (BMAL1) 对于昼夜节律至关重要.
- 在单细胞功能中的BMAL1-PAS域的作用基本上是未知的.
- 单细胞在免疫和炎症中起着关键作用.
研究的目的:
- 研究BMAL1-PAS域在人类单细胞功能中的作用.
- 阐明将BMAL1-PAS与单细胞活动联系起来的分子机制.
- 探索BMAL1-PAS域作为潜在的治疗点.
主要方法:
- 使用了人类单细胞细胞系THP-1和一个BMAL1-PAS-B域缺陷突变 (THP-1#207).
- 评估昼夜基因表达,细胞增殖和代谢活动 (糖解,氧化酸化).
- 分析了脂聚糖 (LPS) 诱导的细胞因子产生 (IL-1β,IL-10) 并进行了定量蛋白质组学.
主要成果:
- BMAL1-PAS-B 缺陷取消了昼夜基因表达,并降低了增殖和细胞能量.
- 在LPS刺激后,BMAL1-PAS-B缺乏细胞显示IL-1β减少,IL-10产生增加.
- 蛋白质组学揭示了新陈代谢酶表达的改变,特别是降低了2 (HK2),一个关键的糖解酶. 用2-脱氧-D-葡萄糖 (2-DG) 抑制HK2模仿了这些细胞表型.
结论:
- BMAL1-PAS-B 域对于调节单细胞增殖,细胞能量和炎症反应至关重要.
- 糖解活性,特别是HK2表达,是单细胞中BMAL1-PAS-B域功能的关键媒介.
- BMAL1-PAS-B 域代表了一个有前途的药理学标,用于调节炎症.
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