SHEAR-STRESS MODULATES ENDOTHELIAL-CELL MORPHOLOGY AND F-ACTIN ORGANIZATION THROUGH THE REGULATION OF FOCAL ADHESION-ASSOCIATED PROTEINS

SHEAR-STRESS MODULATES ENDOTHELIAL-CELL MORPHOLOGY AND F-ACTIN ORGANIZATION THROUGH THE REGULATION OF FOCAL ADHESION-ASSOCIATED PROTEINS
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DOI:
10.1002/jcp.1041630121
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发表时间:
1995-04-01
影响因子:
5.6
通讯作者:
NEREM, RM
NEREM, RM
中科院分区:
生物学2区
文献类型:
--
作者:
GIRARD, PR;NEREM, RM

文献摘要

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血流相关的剪切应力已被证明可以调节内皮细胞的结构和功能,包括f -肌动蛋白微丝的组织。局灶黏附相关蛋白,如血管蛋白、talin和特异性整合素可能在这些细胞骨架和形态变化的调节中发挥作用。双标记免疫荧光研究表明,在静态培养中,α (5) β(1)纤维连接蛋白受体(α (5) β (1) FNRs)和α (v) β(3)玻璃体连接蛋白受体(α (v) β (3) VNRs)主要存在于牛主动脉内皮细胞(BAECs)的外周区域,与血管蛋白、talin和肌动蛋白微丝末端的定位相对应。作为对剪切应力的响应,伴随着细胞伸长和与流动方向一致的应力纤维的出现,血管蛋白和α (v) β (3) VNRs作为细胞的“上游”端显著定位。在这些黏附相关蛋白的浓度下,应力纤维的终止是明显的。这些数据表明,这些蛋白质的上游浓度可能直接剪切应力诱导应力纤维的形成,并可能在纤维在流动方向上的排列中起作用。表面α (v) β (3) VNRs的水平在对血流的反应中下降,可能反映了“下游”受体数量的减少。与暴露于流动后观察到的vinculin和α (v) β (3) VNRs的排列不同,talin和α (5) β (1) FNRs除了定位于细胞的上游端外,还均匀分布在细胞的其余部分。α (5) β (1) FNRs的表面水平随着剪切应力的增加而增加,这可能通过这些受体增加了baec对细胞外基质的粘附性。这些数据表明,局灶黏附相关蛋白在baec对剪切应力的反应中起着特定的作用。(C) 1995 Wiley-Liss, Inc。
Flow-related shear stress has been shown to modulate endothelial cell structure and function including F-actin microfilament organization. Focal adhesion-associated proteins such as vinculin, talin, and specific integrins may play a role in the modulation of these cytoskeletal and morphological changes. Double-label immunofluorescence studies indicated that, in static culture, alpha(5) beta(1) fibronectin receptors (alpha(5) beta(1) FNRs) and alpha(v) beta(3) vitronectin receptors (alpha(v) beta(3) VNRs) were found predominantly in the peripheral regions of bovine aortic endothelial cells (BAECs) corresponding to the localization of vinculin, talin, and actin microfilament terminations. in response to shear stress, concomitant with cell elongation and the appearance of stress fibers aligned with the direction of flow, there was a prominent localization of vinculin and alpha(v) beta(3) VNRs as the ''upstream'' end of the cells. Stress fiber terminations were clearly evident at these concentrations of focal adhesion-associated proteins. These data suggest that the upstream concentration of these proteins may direct shear stress-induced stress fiber formation and may function in the alignment of the fibers in the direction of flow. Levels of surface alpha(v) beta(3) VNRs were found to decrease in response to flow, possibly reflecting the decrease in numbers of ''downstream'' receptors. Unlike the arrangement of vinculin and alpha(v) beta(3) VNRs observed following exposure to flow, talin and alpha(5) beta(1) FNRs, in addition to being localized at the upstream end of the cell, were also evenly distributed throughout the rest of the cell. Surface levels of alpha(5) beta(1) FNRs increased in response to shear stress, perhaps providing an increased adherence of BAECs to the extracellular matrix through these receptors. These data suggest that focal adhesion-associated proteins play specific roles in the response of BAECs to shear stress. (C) 1995 Wiley-Liss, Inc.