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血液动力力通过MIEN1-ERK/MAPK信号轴来决定内皮血管生成
Lin Cheng1, Huiyu Shi1, Lingyu Du1
1West China School of Basic Medical Sciences & Forensic Medicine, Institute of Biomedical Engineering, Sichuan University, Chengdu, China.
Journal of cellular physiology
|January 12, 2024
概括
扰乱剪切应激 (DSS) 通过降低血管内皮生长因子B (VEGFB) 的调节来损害血管生成. 膜蛋白MIEN1调节ERK/MAPK信号传递和细胞骨组织,在不同的流量条件下影响内皮血管生成.
科学领域:
- 心血管生物学 心血管生物学
- 机械生物学 机械生物学
- 内皮细胞功能 内皮细胞功能
背景情况:
- 血液流动模式,特别是动脉分支的干扰剪切应力 (DSS),与动脉样硬化有关.
- 流动产生的流体剪切应力 (FSS) 对于血管新生在伤口愈合和组织修复中至关重要.
- 内皮细胞感知并响应不同的FSS模式以调节血管生成的精确机制尚未完全理解.
研究的目的:
- 为了研究层状剪切应力 (LSS) 和扰乱剪切应力 (DSS) 如何差异调节内皮血管生成.
- 阐明特定分子参与者的作用,如MIEN1,在调解内皮对FSS的反应.
- 了解涉及剪切压力诱导血管生成的信号通路.
主要方法:
- 在内皮细胞中应用了层状剪切应力 (LSS,15dyn/cm2) 和扰乱剪切应力 (DSS,0.5±4dyn/cm2).
- 评估血管生成,血管内皮生长因子B (VEGFB) 表达,以及膜蛋白MIEN1.1的变化.
- 分析ERK/MAPK信号通路和MIEN1指导的细胞骨组织.
主要成果:
- 与LSS相比,DSS显著损害了血管新生和下调的内源VEGFB表达.
- 发现膜蛋白MIEN1的变化在调节ERK/MAPK信号传递方面起作用.
- 证明MIEN1参与了剪切压力诱导的细胞骨组织,影响内皮血管生成.
结论:
- 截然不同的FSS模式可以差异调节内皮血管生成.
- MIEN1是内皮对FSS反应的关键调解者,通过ERK/MAPK信号和细胞骨动力学影响血管生成.
- 了解这些机制对于理解血管生成在从生理向病理血流过渡期间发生的变化至关重要.
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