内源性蛋白 C 对于维持人内皮细胞的功能完整性是必需的。
Endogenous protein C is essential for the functional integrity of human endothelial cells.
机构信息
Sutton Research Laboratories, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, Level 10, The Kolling Building, St Leonards, NSW 2065, Australia.
出版信息
Cell Mol Life Sci. 2010 May;67(9):1537-46. doi: 10.1007/s00018-010-0269-y. Epub 2010 Feb 3.
Abstract
Circulating protein C (PC) plays a vital role as an anti-coagulant and anti-inflammatory mediator. We show here that human endothelial cells produce PC that acts through novel mediators to enhance their own functional integrity. When endogenous PC or its receptor, endothelial protein C receptor (EPCR), was suppressed by small interfering (si) RNA, human umbilical cord endothelial cell (HUVEC) proliferation was decreased and apoptosis elevated. Interestingly, PC or EPCR siRNA significantly increased HUVEC permeability, which is likely via reduction of the angiopoietin (Ang)1/Ang2 ratio and inhibition of the peripheral localization of the tight junction protein, zona occludins-1. In addition, PC or EPCR siRNA inhibited type IV collagen and matrix metalloproteinase-2, providing the first evidence that PC contributes to vascular basement membrane formation. These newly described actions of endogenous PC act to stabilize endothelial cells and enhance barrier function, to potentially promote the functional integrity of blood vessels.
摘要
循环蛋白 C (PC) 作为一种抗凝血剂和抗炎介质发挥着至关重要的作用。我们在这里表明，人内皮细胞产生 PC，通过新型介质发挥作用，增强其自身的功能完整性。当内源性 PC 或其受体内皮蛋白 C 受体 (EPCR) 被小干扰 (si) RNA 抑制时，人脐静脉内皮细胞 (HUVEC) 的增殖减少，凋亡增加。有趣的是，PC 或 EPCR siRNA 显著增加了 HUVEC 的通透性，这可能是通过降低血管生成素 (Ang)1/Ang2 比值和抑制紧密连接蛋白封闭蛋白-1 的外周定位来实现的。此外，PC 或 EPCR siRNA 抑制了 IV 型胶原和基质金属蛋白酶-2，这为 PC 有助于血管基底膜形成提供了第一个证据。内源性 PC 的这些新描述的作用作用是稳定内皮细胞并增强屏障功能，从而可能促进血管的功能完整性。
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