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HUMAN TISSUE FACTOR AND ITS PLASMA INHIBITOR

人体组织因子及其血浆抑制剂

基本信息

批准号：
6388973
负责人：
GEORGE J BROZE
金额：
$ 36.93万
依托单位：
BARNES-JEWISH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 2003-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6388973
关键词：
activation product blood coagulation coagulation factor VII disease /disorder model genotype human tissue intermolecular interaction laboratory mouse laboratory rabbit low density lipoprotein phenotype protease inhibitor protein binding protein structure function thromboplastin tissue /cell culture

项目摘要

DESCRIPTION: (Investigator's abstract) Tissue factor pathway inhibitor (TFPI) is a critical regulator of tissue factor induced coagulation. The overall goals of this proposal are to further delineate the structures within the TFPI molecule that mediate its specific functional properties and to better define the physiologic role of TFPI through the use of mouse models. The specific aims are: 1) determine the structure of 34 kDa TFPI bound in plasma by low density lipoproteins (LDL) and determine the mechanisms underlying this association; 2) investigate the mechanisms of TFPI association with cell surfaces by examining the structure and properties of a mammalian expressed rTFPI which lacks this attribute; 3) further characterize TFPIK1 gene-disrupted mice which have an isolated deficiency in TFPI-mediated factor VIIa/TF inhibition; 4) produce TFPI null mice and compare their phenotype with that of TFPIK1 mice; and 5) attempt to rescue TFPIK1 (-/-) mice from intrauterine mortality with doxycycline-regulated transgene expression of TFPI to permit the evaluation of the physiologic role of TFPI in adult animals.

描述：（研究者摘要）组织因子途径抑制剂 TFPI是组织因子诱导的凝血的关键调节因子。的本提案的总体目标是进一步界定在TFPI分子内，介导其特定的功能特性，为了更好地定义TFPI的生理作用，通过使用小鼠模型具体目的是：1）确定34 kDa TFPI的结构血浆中低密度脂蛋白（LDL）的结合，并确定这种关联的机制; 2）调查的机制通过检查TFPI与细胞表面的结构和缺乏该属性的哺乳动物表达的rTFPI的性质; 3）进一步表征TFPIK 1基因破坏的小鼠，其具有分离的 TFPI介导的因子VIIa/TF抑制的缺陷; 4）产生TFPI无效小鼠，并将它们表型与TFPIK 1小鼠的表型进行比较;和5）试图用以下方法拯救TFPIK 1（-/-）小鼠免于宫内死亡：多西环素调节TFPI的转基因表达，以允许评估 TFPI在成年动物中的生理作用。

项目成果

期刊论文数量（39）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The low density lipoprotein receptor-related protein mediates the cellular degradation of tissue factor pathway inhibitor.

DOI：
10.1073/pnas.91.14.6664
发表时间：
1994-07
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
I. Warshawsky;G. Broze;A. Schwartz
通讯作者：
I. Warshawsky;G. Broze;A. Schwartz

Physiological concentrations of tissue factor pathway inhibitor do not inhibit prothrombinase.