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

血液流动性的分子生物学研究——抗凝蛋白C通路内皮受体的结构与功能关系

• 批准号: 09480149
• 负责人: SUZUKI Koji
• 金额: $ 8.32万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480149/
• 关键词: protein C pathway; protein C; protein S; protein C inibitor; blood fluidity mechanism; endothelial cells; protein C receptor; protein S receptor; 抗血栓性因子; 血液凝固因子; トロンボモジュリン; 細胞膜受容体; 抗血栓性機構; 血液流動性機構; 遺伝子発現調節; 血栓症; トロンボモジュリン異常症; プロテインC受容体異常症

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.

抗凝蛋白C通路是维持血管血液流动性的重要系统之一。本课题旨在阐明抗凝蛋白C通路中几种内皮受体的结构与功能关系，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）人内皮蛋白C受体（EPCR）基因的分子克隆。(2)人蛋白C抑制剂（PCI）基因表达的分子机制，特别是在肝细胞中。(3)人血小板α颗粒分泌PCI调节活性的表达机制(4)PCI的结构-功能关系及其组织特异性mRNA表达在不同物种中的差异;人、猴、兔、牛、大鼠和小鼠。(5)参与抗凝蛋白C途径的因子在与各种疾病相关的发病机制中的作用。(6)腺苷和NO维持内皮细胞抗凝血能力的分子机制。（7）凝血酶和凝血酶原对肿瘤细胞转移的影响。(8)人血管内皮细胞S蛋白受体的鉴定和分离。这些研究可能突出了抗凝蛋白C途径对血液流动性的作用机制。

项目成果

Kise, H.: "Measurement of protein C inhibitor in seminal plasma is useful for detecting agenesis of seminal vesicles or the vas defens"J. Andrology. 21. 207-212 (2000)

Kise, H.：“精浆中蛋白 C 抑制剂的测量对于检测精囊或输精管发育不全非常有用”J.

Takagi, M.: "Increased activated protein C : protein C inhibitor complex levels in patients with chroni renal failure on maintenance hemodialysis"Clin. Appl. Thromb. Hemost.. 5. 113-116 (1999)

Takagi, M.：“维持性血液透析慢性肾功能衰竭患者的活化蛋白 C：蛋白 C 抑制剂复合物水平升高”Clin。

Hayashi, T., et al.: "Regulation of the human protein C inhibitor gene expression in HepG2 cells : Role of Sp1 and AP2"Biochem. J.. 332. 573-578 (1998)

Hayashi, T. 等人：“HepG2 细胞中人蛋白 C 抑制剂基因表达的调节：Sp1 和 AP2 的作用”Biochem。

Usui,M., Hayashi,T., Suzuki,K., et al.: "Canine lipopolysaccharide-binding protein:cDNA cloning and its tissue distribution of canine model of extended hepatectomy." Biochim.Biophys.Acta. (in press). (1998)

Usui,M., Hayashi,T., Suzuki,K., et al.：“犬脂多糖结合蛋白：犬扩大肝切除模型的 cDNA 克隆及其组织分布。”

Deguchi,H., Takeya,H., Suzuki,K., et al.: "Kringle I domain of prothrombin interacts with factor Va during the assembly of the prothrombinase complex." Biochem.J.321. 729-735 (1997)

Deguchi,H.、Takeya,H.、Suzuki,K. 等人：“凝血酶原的 Kringle I 结构域在凝血酶原酶复合物组装过程中与因子 Va 相互作用。”