Platelet endothelial cell adhesion molecule-1 and mechanotransduction in vascular endothelial cells

Platelet endothelial cell adhesion molecule-1 and mechanotransduction in vascular endothelial cells
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DOI:
10.1111/j.1365-2796.2006.01623.x
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发表时间:
2006-04-01
影响因子:
11.1
通讯作者:
Fujiwara, K
Fujiwara, K
中科院分区:
医学1区
文献类型:
--
作者:
Fujiwara, K

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已知内皮细胞响应于机械力,例如流体剪切应力和循环拉伸,但是阐明机械传感的机制一直是困难的。实验数据表明,可能有几种传感机制。我们最近提出了一种新的机械反应机制,涉及血小板内皮细胞粘附分子-1(PECAM-1)。当内皮细胞受到流体剪切应力刺激时,PECAM-1被酪氨酸磷酸化并激活细胞外信号调节激酶1和2(ERK 1/2)信号级联反应。当我们使用涂有抗PECAM-1外部结构域的抗体的磁珠直接对内皮细胞表面上的PECAM-1施加拉力时,发生了相同的信号传导事件。这些结果似乎表明PECAM-1是一种机械转导分子。据我们所知,这是第一个显示出对直接施加于其上的机械力作出反应的哺乳动物分子。
Endothelial cells are known to respond to mechanical forces such as fluid shear stress and cyclic stretch, but elucidating the mechanism for mechanosensing has been difficult. Experimental data indicate that there are probably several sensing mechanisms. We have recently proposed a novel mechanoresponse mechanism that involves platelet endothelial cell adhesion molecule-1 (PECAM-1). When endothelial cells are stimulated by fluid shear stress, PECAM-1 is tyrosine phosphorylated and activates the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling cascade. The same signalling events occurred when we applied pulling force directly on PECAM-1 on the endothelial cell surface using magnetic beads coated with antibodies against the external domain of PECAM-1. These results appear to indicate that PECAM-1 is a mechanotransduction molecule. To our knowledge, this is the first mammalian molecule that is shown to respond to mechanical force directly exerted to it.