Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production.

Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production.
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DOI:
10.1038/s41598-021-90941-w
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发表时间:
2021-05-31
期刊:
影响因子:
4.6
通讯作者:
Tarbell JM
Tarbell JM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bartosch AMW;Mathews R;Mahmoud MM;Cancel LM;Haq ZS;Tarbell JM

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本研究旨在阐明glypican-1和PECAM-1在剪切诱导内皮细胞产生一氧化氮中的作用。采用原子力显微镜对人脐静脉内皮细胞表面的glypican-1和PECAM-1施加力,并使用荧光报告染料测量一氧化氮。Glypican-1牵拉30分钟刺激一氧化氮产生,而PECAM-1牵拉则没有。然而,PECAM-1下游激活对于glypican-1力诱导反应是必要的。Glypican-1敲除小鼠表现出血流诱导的eNOS磷酸化受损,而PECAM-1的表达没有改变。本文阐明了流体剪切应力对一氧化氮产生的机械转导的合作机制,其中glypican-1感知血流并磷酸化PECAM-1,导致内皮一氧化氮合酶磷酸化和一氧化氮产生。
This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress to nitric oxide production was elucidated in which glypican-1 senses flow and phosphorylates PECAM-1 leading to endothelial nitric oxide synthase phosphorylation and nitric oxide production.
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