已激活的第七因子与组织因子结合,通过细胞外信号调节的激酶激活触发平滑肌细胞的增殖
Plinio Cirillo1, Gaetano Calì, Paolo Golino
1Division of Cardiology, University of Naples Federico II, Italy.
Circulation
|June 3, 2004
概括
激活的因子VII (FVIIa) 与平滑肌细胞上的组织因子 (TF) 结合,通过非凝固途径触发增殖,激活ERK信号级联.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 血管生物学 血管生物学
背景情况:
- 组织因子 (TF) 启动凝血,但也可以作为细胞受体.
- 目前正在研究TF在信号传导和细胞增殖中的作用.
研究的目的:
- 为了确定与TF结合的激活因子VII (FVIIa) 是否刺激光滑肌细胞 (SMC) 增殖.
- 阐明参与FVIIa诱导的SMC扩散的细胞内机制.
主要方法:
- 通过 [3H] 提米丁的结合和细胞计数来评估SMC的扩散.
- 利用活性位点抑制的FVIIa (FVIIai) 和抗TF抗体来研究特异性.
- 分析了p44/42中位素激活蛋白 (MAP) 激酶 (ERK 1/2) 途径通过西区血栓激活的情况.
- 使用MEK抑制剂 (UO126) 来确认ERK通路的作用.
主要成果:
- 剂量依赖的FVIIa诱导了SMC的扩散,FVIIai和一种反TF抗体阻止了这种扩散.
- 将FVIIa与TF结合激活了ERK1/2通路,由ERK酸化证明.
- 通过FVIIai或反-TF抗体治疗,扩散和ERK酸化被废除.
- 抑制MEK抑制了FVIIa诱导的SMC扩散,证实了ERK通路的参与.
结论:
- FVIIa对SMC的TF具有约束力,通过凝固独立的机制特别诱导扩散.
- 这种相互作用激活了ERK 1/2信号通路.
- 这些发现表明凝血,炎症和动脉样硬化之间存在新的联系.
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