微管稳定开关改变了隔离的血管光滑肌 Ca2+ 流量,以应对矩阵刚性
Robert T Johnson1,2, Finn Wostear1,2, Reesha Solanki1,2
1School of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
Journal of cell science
|September 20, 2024
概括
血管光滑肌细胞 (VSMC) 体积和 (Ca2+) 流量由微管稳定性控制,该稳定性对矩阵刚度有反应. 操纵微管稳定性可以改变VSMC对大动脉壁衰老的反应.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 生物医学工程 生物医学工程
背景情况:
- 衰老会增加大动脉壁矩阵的刚性,促使血管光滑肌细胞 (VSMCs) 产生更大的收缩力.
- 增加的矩阵刚性增加了VSMC的数量,但根本的监管机制尚未完全理解.
研究的目的:
- 调查微管稳定性在调节VSMC体积和Ca2+流量中对矩阵刚性的作用.
- 阐明将矩阵刚性,微管子动态和VSMC机械传导联系在一起的机制.
主要方法:
- 使用具有不同刚性的水凝基板来模仿柔性和刚性的细胞外基质.
- 在不同的矩阵刚性条件下,研究了VSMC反应,包括体积和Ca2+流量.
- 研究了微管稳定和不稳定剂以及HDAC6破坏对VSMC行为的影响.
主要成果:
- 增强的矩阵刚性通过Piezo1-介导的Ca2+流入减少了VSMC中的微管稳定性.
- 微管动力学调节了VSMC体积和Ca2+流量;稳定性降低了它们在刚性基板上,而不稳定性增加了它们在柔性基板上.
- HDAC6 干扰增加了可性水凝上的α-tubulin 乙化,VSMC 体积和Ca2+ 流量,但不影响微管稳定性.
结论:
- 微管稳定开关通过控制Ca2+流量来调节VSMC体积,以应对矩阵刚度.
- 微管稳定性是VSMC机械传导的关键调节器,并为修改VSMC应答在衰老的血管系统提供了潜在的目标.
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