Shear stress augments the endothelial cell differentiation marker expression in late EPCs by upregulating integrins
Shear stress augments the endothelial cell differentiation marker expression in late EPCs by upregulating integrins
复制标题
剪切应力通过上调整合素来增强晚期 EPC 中内皮细胞分化标志物的表达。
DOI：
10.1016/j.bbrc.2012.07.115
复制
发表时间：
2012-08-24
影响因子：
3.1
通讯作者：
Cheng, Min
中科院分区：
文献类型：
--
作者：
Cui, Xiaodong;Zhang, Xiaoyun;Cheng, Min
血管内皮细胞损伤与动脉粥样硬化的发生有关。大量研究表明，内皮祖细胞（EPCs），特别是晚期EPCs，在内皮细胞的维持和修复中发挥重要作用。最近的证据表明，切应力是EPC分化的关键调节因子。然而，详细的事件，有助于剪切应力诱导的EPC分化，特别是机械转导的机制，仍有待确定。本研究旨在进一步证实切应力对EPC晚期分化的影响，并探讨整合素在此过程中的作用。观察到切应力增加了从大鼠骨髓分离的晚期EPCs中内皮细胞分化标志物（例如vWF和CD 31）的表达。此外，剪切应力增强了整合素亚基p和p的mRNA表达，在一个时间依赖性的方式，也上调了特定的整合素在晚EPCs板上含有各种细胞外基质（ECM）蛋白的基板。此外，发现剪切应力诱导的vWF和CD 31表达与整合素β（1）和β（3）的水平相关，并且在用阻断整合素与细胞外基质结合的RGD肽（Gly-Arg-Gly-Asp-Asn-Pro，GRGDNP）处理的晚期EPC中被抑制。此外，这种增加也被抗β（1）整联蛋白和抗β（3）整联蛋白抗体减弱。因此，整合素亚基β（1）和β（3）在调节晚期EPCs中剪切应力诱导的内皮细胞分化标志物表达中起重要作用。这可能提供了新的见解机械力转导机制的剪切应力介导的晚期EPC分化。(c)2012 Elsevier Inc. All rights reserved.
Vascular endothelial cell injury has been implicated in the onset of atherosclerosis. A number of previous studies have demonstrated that endothelial progenitor cells (EPCs), in particular late EPCs, play important roles in endothelial maintenance and repair. Recent evidence has revealed shear stress as a key regulator for EPC differentiation. However, the detailed events that contribute to the shear stress-induced EPC differentiation, in particular the mechanisms of mechanotransduction, remain to be identified. The present study was undertaken to further confirm the effects of shear stress on the late EPC differentiation, and to investigate the role of integrins in this procedure. Shear stress was observed to increase the expression of endothelial cell differentiation markers, such as vWF and CD31, in late EPCs isolated from rat bone marrow. Shear stress moreover enhanced the mRNA expression of integrin subunits p, and p, in a time-dependent manner, and also upregulated specific integrins in late EPCs plated on substrates containing various extracellular matrix (ECM) proteins. In addition, the shear stress-induced vWF and CD31 expression were found to be related to the levels of integrin beta(1) and beta(3), and were inhibited in late EPCs treated with RGD peptide (Gly-Arg-Gly-Asp-Asn-Pro, GRGDNP) that blocks the binding of integrins to the extracellular matrix. Additionally, this increase was also attenuated by both anti-beta(1) integrin and anti-beta(3) integrin antibodies. The integrin subunits beta(1) and beta(3) thus play important roles in regulating the shear stress-induced endothelial cell differentiation marker expression in late EPCs. This may provide novel insights into the mechanisms of mechanotransduction in shear stress-mediated late EPC differentiation. (c) 2012 Elsevier Inc. All rights reserved.