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首页> 外文期刊>Cytokine >CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced endothelial cell migration.
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CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced endothelial cell migration.

机译:CXCR1和CXCR2是介导层流剪切应力诱导的内皮细胞迁移的新型机械传感器。

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摘要

The migration of endothelial cells (ECs) plays critical roles in vascular physiology and pathology. The receptors CXCR1 and CXCR2, known as G protein-coupled receptors which are essential for migratory response of ECs toward the shear stress-dependent CXCL8 (interleukin-8), are potential mechano-sensors for mechanotransduction of the hemodynamic forces. In present study, the mRNA and protein expression of CXCR1 and CXCR2 in EA.hy926 cells was detected by RT-PCR and Western blot analysis under three conditions of laminar shear stress (5.56, 10.02 and 15.27 dyn/cm(2)) respectively. Using a scratched-wound assay, the effects of CXCR1 and CXCR2 were assessed by the percentage of wound closure while CXCR1 and CXCR2 were functional blocked by the CXCL8 receptor antibodies. The results showed that the mRNA and protein expression of CXCR1 and CXCR2 was both upregulated by 5.56 dyn/cm(2) laminar shear stress, but was both downregulated by 15.27 dyn/cm(2). The wound closure was inhibited significantly while cells were treated with those antibodies in all the conditions. It was suggested that CXCR1 and CXCR2 are involved in mediating the laminar shear stress-induced EC migration. Taken together, these findings indicated that CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced EC migration. Understanding this expanded mechanism of laminar shear stress-induced cell migration will provide novel molecular targets for therapeutic intervention in cancer and cardiovascular diseases.
机译:内皮细胞(ECs)的迁移在血管生理和病理中起着至关重要的作用。受体CXCR1和CXCR2,即G蛋白偶联受体,对于EC对依赖剪切应力的CXCL8(interleukin-8)的迁徙反应必不可少,是潜在的机械传感器,可进行血流动力学力的机械传导。在本研究中,通过RT-PCR和Western blot分析在层流剪切应力的三种条件下(5.56、10.02和15.27 dyn / cm(2))分别检测EA.hy926细胞中CXCR1和CXCR2的mRNA和蛋白表达。使用划伤试验,通过伤口闭合的百分比评估CXCR1和CXCR2的效果,而CXCR1和CXCR2被CXCL8受体抗体功能性阻断。结果表明,CXCR1和CXCR2的mRNA和蛋白表达均被5.56 dyn / cm(2)层流切应力上调,但均被15.27 dyn / cm(2)上调。在所有条件下用这些抗体处理细胞时,伤口闭合均受到明显抑制。有人建议CXCR1和CXCR2参与介导层流剪切应力诱导的EC迁移。综上所述,这些发现表明CXCR1和CXCR2是介导层流剪切应力诱导的EC迁移的新型机械传感器。了解层流剪切应力诱导的细胞迁移的这种扩展机制将为癌症和心血管疾病的治疗干预提供新的分子靶标。

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