The roles of the COXs in normal physiology and in pathological conditions

COX 在正常生理和病理条件下的作用

基本信息

批准号：
7967956
负责人：
Robert Langenbach
金额：
$ 46.78万
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7967956
关键词：
Abdomen Adult Aneurysm Appearance Attenuated Blood Vessels Brain Cell Differentiation process Cells Cellular Structures Development Endothelial Cells Goals Heart In Vitro Individual Inflammatory Response Laboratories Measures Mus PTGS2 gene Physiology Protein Isoforms Role Staining method Stains System Vascular Endothelial Growth Factor Receptor cyclooxygenase 1 embryonic stem cell inhibitor/antagonist mouse model

Abdomen Adult Aneurysm Appearance Attenuated Blood Vessels Brain Cell Differentiation process Cells Cellular Structures Development Endothelial Cells Goals Heart In Vitro Individual Inflammatory Response Laboratories Measures Mus PTGS2 gene Physiology Protein Isoforms Role Staining method Stains System Vascular Endothelial Growth Factor Receptor cyclooxygenase 1 embryonic stem cell inhibitor/antagonist mouse model

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项目摘要

The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states. Specifically, effort within the laboratory has focused on using COX-2 deficient mouse ES cells and COX specific inhibitors to study the roles of COX-2 in endothelial cell development and aneurysm formation. Endothelial cell ifferentiation was measured immunohistochemically by the appearance of CD-31 staining cord like structures of cells and the appearance of VEGF receptors and COX-2 on Western analysis. Our studies indicated that the deficiency of COX-2 inhibited mouse ES cell differentiation into endothelial-like cells in vitro. However, studies with COX-2 selective inhibitors have indicated that the COX-2 inhibitors blocked endothelial-like cell development even in COX-2-/- ES cells, suggesting that a COX-2 independent mechanism was responsible. In addition, a mouse model to study the contributions of COX-2 to aneurysm formation is being developed and initial studies indicate that COX-2 deficiency attenuates inflammatory responses in the mouse heart and abdominal vasculature. Also, collaborative studies have demonstrated that COX-2 deficiency increased inflammatory responses in the mouse brain.

这些研究的主要目标是阐明COX-1和COX-2在正常生理和各种病理状态中的各个角色。具体而言，实验室内的努力集中在使用COX-2缺陷的小鼠ES细胞和COX特异性抑制剂来研究COX-2在内皮细胞发育和动脉瘤形成中的作用。通过CD-31染色线（如细胞的结构）以及VEGF受体的出现以及在西方分析中的COX-2的出现，通过出现CD-31染色绳的外观来测量内皮细胞的iffertiation。我们的研究表明，COX-2的缺乏在体外抑制了小鼠ES细胞细胞分化为内皮样细胞。然而，对COX-2选择性抑制剂的研究表明，COX-2抑制剂即使在COX-2 - / - ES细胞中也阻塞了内皮样细胞的发育，这表明COX-2独立机制是造成的。此外，正在开发研究COX-2对动脉瘤形成的贡献的小鼠模型，并初步研究表明COX-2缺乏衰减小鼠心脏和腹部脉管系统中的炎症反应。此外，协作研究表明，COX-2缺乏增加了小鼠大脑的炎症反应。