Extracellular matrix fibronectin mediates an endothelial cell response to shear stress via the heparin-binding, matricryptic RWRPK sequence of FNIII1H.
Extracellular matrix fibronectin mediates an endothelial cell response to shear stress via the heparin-binding, matricryptic RWRPK sequence of FNIII1H.
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细胞外基质纤连蛋白通过 FNIII1H 的肝素结合、基质隐性 RWRPK 序列介导内皮细胞对剪切应力的反应。
DOI：
10.1152/ajpheart.00126.2016
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Sarelius,IngridH
中科院分区：
文献类型：
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作者：
Okech,William;Abberton,KerenM;Kuebel,JuliaM;Hocking,DeniseC;Sarelius,IngridH
内皮细胞（EC）以多种方式对切应力等机械力做出反应，其中之一是细胞骨架沿流动方向重新排列。我们早期的研究涉及细胞外基质蛋白纤连蛋白在机械感觉信号传导到EC在完整的小动脉，通过依赖于肝素结合区的第一个III型重复的纤维状纤连蛋白（FNIII 1H）的信号通路。在这里，我们测试的假设，FNIII 1H是需要EC应力纤维重新排列下流。人脐静脉内皮细胞（HUVEC）暴露于规定的流动条件被用作一个良好的表征模型，这种应力纤维排列响应。我们的研究结果直接牵连FNIII 1H在重新排列的应力纤维在HUVEC，重要的是，表明matricryptic肝素结合RWRPK序列位于FNIII 1的反应是必需的。此外，我们发现，在不存在FHIII 1H的情况下，通过α5β1-整合素特异性配体粘附的EC中流动介导的应力纤维重新排列不会发生，相反，在流动下αvβ3-整合素介导的应力纤维重新排列不需要FNIII 1H。因此，我们的研究结果表明，有两个独立的机械信号通路介导的压力纤维的排列后，暴露的EC流动，一个依赖于αvβ3-整合素和依赖于FNIII 1H。这项研究强烈支持的结论是，FNIII 1H的RWRPK区域可能有广泛的能力作为机械感觉信号位点。
Endothelial cells (EC) respond to mechanical forces such as shear stress in a variety of ways, one of which is cytoskeletal realignment in the direction of flow. Our earlier studies implicated the extracellular matrix protein fibronectin in mechanosensory signaling to ECs in intact arterioles, via a signaling pathway dependent on the heparin-binding region of the first type III repeat of fibrillar fibronectin (FNIII1H). Here we test the hypothesis that FNIII1H is required for EC stress fiber realignment under flow. Human umbilical vein ECs (HUVECs) exposed to defined flow conditions were used as a well-characterized model of this stress fiber alignment response. Our results directly implicate FNIII1H in realignment of stress fibers in HUVECs and, importantly, show that the matricryptic heparin-binding RWRPK sequence located in FNIII1 is required for the response. Furthermore, we show that flow-mediated stress fiber realignment in ECs adhered via α5β1-integrin-specific ligands does not occur in the absence of FHIII1H, whereas, in contrast, αvβ3-integrin-mediated stress fiber realignment under flow does not require FNIII1H. Our findings thus indicate that there are two separate mechanosignaling pathways mediating the alignment of stress fibers after exposure of ECs to flow, one dependent on αvβ3-integrins and one dependent on FNIII1H. This study strongly supports the conclusion that the RWRPK region of FNIII1H may have broad capability as a mechanosensory signaling site.