The roles of the COXs in normal physiology and pathology

COXs 在正常生理和病理中的作用

• 批准号: 7161817
• 负责人: Robert Langenbach
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 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/7161817
• 关键词: angiogenesis; bronchial mucus; cell differentiation; cyclooxygenase inhibitors; embryonic stem cell; genetically modified animals; inflammation; laboratory mouse; lung disorder; nonsteroidal antiinflammatory agent; oxidoreductase inhibitor; prostaglandin endoperoxide synthase; protein isoforms; tissue /cell culture; vascular endothelial growth factors; vascular endothelium

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 using the COX deficient mice. Included in these studies are the roles of the COX isoforms in gastric ulceration, lung inflammation and vascular development. Our early studies in COX deficient mice was to investigate gastric ulceration, inflammatory responses and kidney development. More recent interest in the laboratory has been to study the effects of COX deficiency on lung inflammation and mucus production. Additionally, effort within the laboratory has focused on using COX-1 and COX-2 deficient ES cells to study the roles of the COXs in endothelial cell development. Studies suggest that the deficiency of COX-1 or COX-2 do not inhibit ES cell differentiation into endothelial cells. Studies with COX-1 and COX-2 selective inhibitors have been used and the data obtained suggest that the COX-2 inhibitor inhibits epithelial cell development by a COX dependent mechanism.

这些研究的主要目标是阐明使用COX缺乏小鼠在正常生理和各种病理状态中COX-1和COX-2的个体作用。这些研究包括Cox同工型在胃溃疡，肺部炎症和血管发育中的作用。我们对COX缺乏小鼠的早期研究是研究胃溃疡，炎症反应和肾脏发育。对实验室的最新兴趣是研究Cox缺乏对肺部炎症和粘液产生的影响。此外，实验室内的努力集中在使用COX-1和COX-2缺陷ES细胞来研究COX在内皮细胞发育中的作用。研究表明，COX-1或COX-2的缺乏不会抑制ES细胞分化为内皮细胞。已经使用了COX-1和COX-2选择性抑制剂的研究，获得的数据表明，COX-2抑制剂通过COX依赖性机制抑制上皮细胞的发育。