Medicine Research Center, Weifang Medical College, Weifang, Shandong 261053, PR China.
Biochem Biophys Res Commun. 2012 Aug 24;425(2):419-25. doi: 10.1016/j.bbrc.2012.07.115. Epub 2012 Jul 27.
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 β(1) and β(3) 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 β(1) and β(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-β(1) integrin and anti-β(3) integrin antibodies. The integrin subunits β(1) and β(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.
血管内皮细胞损伤与动脉粥样硬化的发生有关。许多先前的研究表明，内皮祖细胞（EPCs），尤其是晚期 EPCs，在维持和修复内皮方面发挥着重要作用。最近的证据表明，切应力是 EPC 分化的关键调节因子。然而，导致切应力诱导的 EPC 分化的详细事件，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晚期 EPC 分化的影响，并探讨整合素在这一过程中的作用。切应力观察到增加从大鼠骨髓分离的晚期 EPC 中内皮细胞分化标志物，如 vWF 和 CD31 的表达。切应力还以时间依赖性方式增强整合素亚基β（1）和β（3）的 mRNA 表达，并在含有各种细胞外基质（ECM）蛋白的基质上培养晚期 EPC 时上调特定整合素。此外，发现切应力诱导的 vWF 和 CD31 表达与整合素β（1）和β（3）的水平有关，并在用 GRGDNP（甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸-脯氨酸）处理的晚期 EPC 中受到抑制，GRGDNP 阻止整合素与细胞外基质的结合。此外，这种增加也被抗β（1）整合素和抗β（3）整合素抗体减弱。整合素亚基β（1）和β（3）因此在调节晚期 EPC 中切应力诱导的内皮细胞分化标志物表达中发挥重要作用。这可能为切应力介导的晚期 EPC 分化中机械转导的机制提供新的见解。
