机械敏感膜领域调节进入动脉内皮细胞,以防止炎症
Soon-Gook Hong1,2, Julianne W Ashby1, John P Kennelly2,3
1Department of Medicine, Division of Cardiology.
The Journal of clinical investigation
|May 21, 2024
概括
对内皮细胞 (ECs) 的高层切割应力激活了极化信号中心. 这种TRPV4通道依赖的机制抑制炎症并增强动脉中的细胞弹性.
科学领域:
- 机械生物学 机械生物学
- 内皮细胞生物学 内皮细胞生物学
- 心血管研究研究心血管研究
背景情况:
- 大动脉中的内皮细胞 (EC) 经历了高剪切压力,促进了抗炎状态.
- 观察到流动诱导的细胞延长和极性,但它们在抗炎性表型中的作用尚不清楚.
研究的目的:
- 调查在高层切割应力下EC中极化信号枢纽的作用.
- 为了确定短暂受体潜在化物4 (TRPV4) 通道在EC抗炎反应中的参与.
主要方法:
- 在连续高层流下,分析EC中高-1-丰富的微域.
- 调查TRPV4通道局部化,与caveolin-1的相互作用,以及 (Ca2+) 信号.
- 对内皮氧化合成酶 (eNOS) 激活和炎症基因表达的评估.
- 使用外源TRPV4激活的体外和体内研究.
主要成果:
- 高流量诱导了高膜刚性和F-actin.富含caveolin-1-丰富的微域的极化.
- 定位在这些微域的TRPV4通道与caveolin-1相互作用,以调节焦点Ca2+的进入.
- 依赖于细胞延长和持续流动的TRPV4信号,激活了eNOS并抑制了炎症基因表达.
- 外源TRPV4激活减少了体外和体内炎症反应.
结论:
- 在动脉EC中存在一个涉及caveolin-1和TRPV4通道的极化机械敏感信号枢纽.
- 这个中心抑制炎症基因表达,并增强了EC对炎症刺激的弹性.
- 在剪切应力下,TRPV4信号传递对于维持ECs的抗炎表型至关重要.
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