Molecular biological studies on the blood fluidity - Structure-function relationship of the endothelial receptors playing in the anticoagulant protein C pathway

抗凝蛋白C途径是维持血管血液流动性的重要系统之一。本项目旨在阐明抗凝蛋白C通路中几种内皮受体的结构-功能关系，以了解血液流动性的分子机制。本文主要研究了以下8个课题：(1)人内皮蛋白C受体（EPCR）基因的分子克隆。(2)人蛋白C抑制剂（PCI）基因在肝细胞中表达的分子机制。(3)人血小板α颗粒分泌PCI调控活性的表达机制。(4)不同物种PCI的结构-功能关系及其组织特异性mRNA表达差异；人类、猴子、兔子、牛、大鼠和小鼠。(5)抗凝蛋白C通路相关因子在各种疾病相关发病机制中的作用。(6)腺苷和一氧化氮维持内皮抗凝能力的分子机制。(7)凝血酶和凝血酶原对肿瘤细胞转移的影响。(8)人内皮细胞蛋白S受体的鉴定与分离。这些研究可能突出了抗凝蛋白C途径影响血液流动性的机制。

The anticoagulant protein C pathway is one of the most important systems to maintain the vascular blood fluidity. The aim of this project is to clarify the structure-function relationship of the several endothelial receptors playing in the anticoagulant protein C pathway to understand the molecular mechanism of the blood fluidity. Here we studied the following eight subjects : (1) Molecular cloning of the human endothelial protein C receptor (EPCR) gene. (2) Molecular mechanism of expression of human protein C inhibitor (PCI) gene, particularly in hepatocyte cells. (3) Mechanism of expression of the regulatory activity of PCI secreted from α granules of human platelets. (4) Structure-function relationship of the PCI and difference of its tissue specific mRNA expression among various species ; humans, monkeys, rabbits, bovines, rats and mice. (5) The role of the factors involved in the anticoagulant protein C pathway in the pathogenesis associated with various diseases. (6) The molecular mechanism to maintain the anticoagulant ability of the endothelium by adenosine and NO. (7) Effect of thrombin on the and prothrombin on the metastasis of tumor cells. (8) Identification and isolation of protein S receptor from human endothelial cells. These studies may highlight the mechanism of blood fluidity by the anticoagulant protein C pathway.