乙酸控制内皮细胞到介质细胞的过渡
Xiaolong Zhu1, Yunyun Wang2, Ioana Soaita3
1Yale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Cell metabolism
|June 16, 2023
概括
内皮细胞的代谢变化驱动EndMT,这是血管疾病的关键过程. 这项研究揭示了酸盐代谢如何激活TGF-β信号,提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 血管生物学 血管生物学
背景情况:
- 内皮转介质转换 (EndMT) 与慢性血管和纤维性疾病有关.
- 终端MT涉及一个积极的反循环与转换生长因子-β (TGF-β) 信号,但其分子驱动器是不清楚的.
研究的目的:
- 阐明TGF-β驱动的EndMT诱导和持久性背后的分子机制.
- 确定慢性血管疾病的新型治疗点.
主要方法:
- 在EndMT期间研究了内皮细胞的代谢变化.
- 分析了乙代谢,PDK4,ACSS2和TGF-β信号元件 (ALK5,SMADs) 的乙化作用.
主要成果:
- 由TGF-β驱动的EndMT是由代谢重编程所支的,特别是从葡萄糖中产生不典型的酸盐.
- 最终MT诱导抑制PDK4,增加了依赖ACSS2的Ac-CoA合成.
- 增加了Ac-CoA乙酸盐ALK5和SMADs,稳定了TGF-β信号传递.
结论:
- 代谢调节,特别是通过ACSS2的酸盐生产和利用,对于EndMT持久性至关重要.
- ACSS2代表了治疗EndMT驱动的慢性血管疾病的潜在治疗标.
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