在Piezo1上,TRPV4主导了高剪切诱导的初始引反应和长期放松
Mohanish K Chandurkar1,2, Manli Yang3, Majid Rostami1,2
1Department of Biomedical Engineering, Michigan Technological University, Houghton, Michigan, United States.
bioRxiv : the preprint server for biology
|February 24, 2025
概括
内皮细胞通过Piezo1和TRPV4离子通道对流体剪切应力 (FSS) 作出反应. TRPV4在最初的引变化和长期放松中起着关键作用,对血管健康和动脉样硬化至关重要.
科学领域:
- 内皮细胞机械生物学
- 血管生理学 血管生理学
- 离子通道功能 离子通道功能
背景情况:
- 内皮细胞对流体剪切应激 (FSS) 的反应对血管健康和动脉样硬化至关重要.
- 之前的研究表明,在高和低FSS下,有明显的引力调节.
- 这些FSS诱导的引反应中介的上游机械传感器以前是未知的.
研究的目的:
- 研究Piezo1和TRPV4离子通道在FSS下调节内皮细胞引力的作用.
- 阐明这些离子通道对内皮细胞机械传导的独特贡献.
主要方法:
- 使用了人类静脉内皮细胞 (HUVECs),具有沉默的Piezo1 (siPiezo1) 和TRPV4 (siTRPV4) 表达.
- 在不同的FSS条件下 (高和低) 测量了内皮细胞的引力.
- 分析了FSS暴露后的引力大小,对齐和时间动态.
主要成果:
- siPiezo1在高FSS下部分降低了初始引力的增加,但没有影响低FSS反应或对齐.
- siTRPV4完全取消了在高和低FSS下的初始引升和对齐.
- 双抑制Piezo1和TRPV4损害了初始和长期的引力,显著增加了低FSS反应,表明了其他途径.
结论:
- 皮埃佐1和TRPV4都是响应FSS的内皮细胞的关键机械传感器.
- 与Piezo1相比,TRPV4在调解最初的引反应和长期放松方面起着更为主导的作用.
- 这些发现凸显了Piezo1和TRPV4对内皮细胞机械转导和血管重塑的独特和关键贡献.
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