指导受体D1是内皮细胞中的机械传感器
Vedanta Mehta1,2, Kar-Lai Pang1,2, Daniel Rozbesky2,3
1Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Nature
|February 7, 2020
概括
素D1 (PLXND1) 作为内皮细胞中的新型机械传感器,检测血流切割压力. 这一发现揭示了一种调节心血管疾病的新机制,
科学领域:
- 心血管生物学
- 机械生物学
- 细胞信号传输
背景情况:
- 血流造成的剪切压力会影响血管健康和疾病,包括动脉样硬化.
- 内皮细胞利用分子机械传感器来解释剪切应力,指导动脉保护性或动脉生成性结果.
- 众所周知是细胞导向的plexins在机械传导中的作用尚未得到研究.
研究的目的:
- 调查素D1 (PLXND1) 在内皮细胞机械感知中的作用及其在机械诱导的心血管疾病中的参与.
- 确定PLXND1是否作为血管系统中的直接剪切应力传感器.
- 阐明PLXND1对剪切应激反应的分子机制.
主要方法:
- 使用内皮细胞的体外和体内研究.
- 对PLXND1应对剪切应力的作用的分析.
- 用神经-1和VEGFR2研究PLXND1复合体的形成.
- 检查PLXND1的分子结构.
主要成果:
- 在体外和体外,Plexin D1 (PLXND1) 对于内皮细胞对剪切应激的反应至关重要.
- PLXND1调节动脉样硬化病变的局部化.
- PLXND1直接感知机械力,并与神经-1和VEGFR2形成一个机械复合体,在结合复合体和整体蛋白的上游.
- 通过不同的分子构造,PLXND1表现为联体或力受体的二元功能.
结论:
- 素D1 (PLXND1) 被确定为内皮细胞中的新型机械传感器,对心血管病理学至关重要.
- PLXND1调解内皮细胞机械敏感性,并影响动脉样硬化的发展.
- 一个单独的受体PLXND1可以通过不同的分子构造来调解细胞对机械刺激的多样性反应.
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