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.

这些研究的主要目的是使用考克斯缺陷小鼠阐明考克斯-1和考克斯-2在正常生理学和各种病理状态中的个体作用。这些研究包括考克斯亚型在胃溃疡、肺部炎症和血管发育中的作用。我们在考克斯缺陷小鼠的早期研究是调查胃溃疡，炎症反应和肾脏发育。实验室最近的兴趣是研究考克斯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于使用考克斯-1和考克斯-2缺陷的ES细胞来研究COX在内皮细胞发育中的作用。研究表明，考克斯-1或考克斯-2的缺陷并不抑制ES细胞向内皮细胞的分化。已使用考克斯-1和考克斯-2选择性抑制剂进行研究，获得的数据表明，考克斯-2抑制剂通过考克斯依赖性机制抑制上皮细胞发育。