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。本项目的目的是阐明几种内皮受体在抗凝蛋白C途径中的结构与功能关系，以了解血液流动性的分子机制。本论文主要研究了以下八个方面的内容：(1)人内皮细胞蛋白C受体基因的分子克隆。(2)人蛋白C抑制物基因表达的分子机制，特别是在肝细胞中的表达。(3)人血小板α颗粒分泌的pCI调节活性的表达机制。(4)人、猴、兔、牛、大鼠、小鼠等不同物种间血管内皮细胞的结构与功能关系及其组织特异性mRNA表达的差异。(5)抗凝蛋白C途径参与的因素在多种疾病发病机制中的作用。(6)腺苷和NO维持血管内皮细胞抗凝能力的分子机制。(7)凝血酶对肿瘤细胞转移和凝血酶原对肿瘤细胞转移的影响。(8)人内皮细胞S受体蛋白的鉴定和分离。这些研究可能通过抗凝蛋白C途径来强调血液流动性的机制。

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.