Mechanotransduction by Endothelial Cells Is Locally Generated, Direction-Dependent, and Ligand-Specific
Mechanotransduction by Endothelial Cells Is Locally Generated, Direction-Dependent, and Ligand-Specific
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DOI：
10.1002/jcp.22125
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发表时间：
2010-08-01
影响因子：
5.6
通讯作者：
Langille, B. Lowell
中科院分区：
文献类型：
--
作者：
Chretien, Marc L.;Zhang, Ming;Langille, B. Lowell
血管内皮细胞对血流施加在其上的剪切应力的变化表现出广泛的反应。感觉机制如何传达有关流动条件的信息以及如何整合这些信息仍然知之甚少。该问题受到以下因素的困扰：（1）大量潜在的力传感器，（2）将这些传感器与信号集成下游位点区分开来的困难，以及（3）理解力如何从细胞顶端表面通过细胞骨架传递到细胞内位点所固有的复杂性。因此，无论是感知力的结构还是加载它们的力的性质都没有被明确定义。在这项研究中，我们采用涂有配体的磁性微球来结合整合素子集（RGD 肽或 I 型胶原蛋白）或 PECAM-1，以区分不同传感器分子的下游信号传导效应以及它们的加载机制。我们发现，对这些跨膜分子施加力会引发生物学上重要的信号传导（ERK1/2、AKT 和 GSK-3 β 磷酸化）以及下游生物反应，这些反应取决于以下两个因素：(1) 传递力的配体和 (2) 施加力的方向。这些发现表明，配体在内皮细胞中局部产生不同的剪切诱导反应，这取决于力的传递方式。 J.细胞。生理学。 224: 352-361, 2010。(C) 2010 Wiley-Liss, Inc.
Vascular endothelial cells display a wide panel of responses to changes in the shear stress that is exerted on them by blood flow. How sensory mechanisms convey information about flow conditions and how this information is integrated remains poorly understood. The issue is confounded by: (1) a large number of potential force sensors, (2) difficulties in differentiating these sensors from downstream sites of signal integration, and (3) the complexities inherent in understanding how forces are transmitted from the apical surface of the cell via the cytoskeleton to intracellular sites. As a consequence, neither the structures that sense force nor the nature of the forces that loads them have been clearly defined. In this study, we employed magnetic microspheres coated with ligands that bind integrin subsets (RGD peptides or type I collagen) or PECAM-1 to discriminate the downstream signaling effects of different sensor molecules and mechanisms for how they are loaded. We found that application of force to these transmembrane molecules elicited biologically important signaling (ERK1/2, AKT, and GSK-3 beta phosphorylation), and downstream biological responses that depended on the following two factors: (1) the ligand that transmitted force and (2) the direction in which force was applied. These findings indicate that ligands locally generate different shear-induced responses in endothelium that depend on how force is delivered. J. Cell. Physiol. 224: 352-361, 2010. (C) 2010 Wiley-Liss, Inc.