DYNAMIC MECHANICAL PERTURBATION AND SIGNAL TRANSDUCTION IN THE AIRWAY EPITHELIUM

气道上皮的动态机械扰动和信号传导

• 批准号: 7954795
• 负责人: TATIANA B KRASIEVA
• 金额: $ 0.09万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954795
• 关键词: Acute; Asthma; Biological Assay; Biotechnology; Cells; Characteristics; Chronic; Collagen; Computer Retrieval of Information on Scientific Projects Database; Deposition; Development; Devices; Endothelin-1; Epithelial; Epithelial Cells; Epithelium; Exposure to; Fibroblasts; Fibronectins; Fibrosis; Funding; Gene Expression; Goals; Grant; Hour; Human; Injury; Institution; Intervention; Laser Scanning Microscopy; Lasers; Lung; Mechanics; Mediator of activation protein; Mesenchymal; Proteins; Research; Research Personnel; Resources; Signal Transduction; Source; Tenascin; Transforming Growth Factors; United States National Institutes of Health; airway epithelium; airway remodeling; bronchial epithelium; cell injury; experience; in vivo; insight; novel; pressure; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is thought that airway narrowing associated with asthmatic episodes results in the transmission of deleterious mechanical forces directly to the bronchial epithelium and it has been shown that these compressive forces augment the release of proinflammatory and profibrogenic mediators from these cells in culture. The additive effect of repeated episodes is thought to induce airway remodeling and collagen deposition by mesenchymal cells of the airway wall resulting in the altered and undesirable airway characteristics seen during asthma. We have developed a device capable of applying compressive forces to epithelial cells in culture thought to be experienced by the pulmonary epithelium during airway narrowing in-vivo, as well as the novel capability of delivering prescribed pressure oscillations that we believe more accurately mimic the forces delivered to the airway epithelium during an acute asthma attack. To characterize these effects, normal human bronchial epithelial (NHLB) cells will be subjected to a single or multiple exposure to 4 hours of static or oscillatory pressures and the media will be assayed for transforming growth factor-¿¿2, endothelin 1 and 2, and fibronectin. Gene expression of these proteins will also be characterized. NHLB cells will then be exposed to the conditions described earlier in the presence of normal human lung fibroblasts (NHLF) to characterize the epithelial-mesenchymal relationship during compression induced cell injury. Gene expression of collagen (I, III and V), tenascin and fibronectin will be assessed and multiphoton laser scanning microscopy will be utilized to quantify collagen deposition by NHLF cells in culture. This study will allow us to examine the effects of compression induced cell injury on the bronchial epithelium and will provide insight into the epithelial-mesenchymal relationship during asthma related injury and its involvement in the development of fibrosis. The ultimate goal of these studies is to aid in the development of pharmacologic interventions to impede the progression of airway remodeling and fibrosis during chronic asthma.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 据认为，与哮喘发作相关的气道狭窄导致有害的机械力直接传递至支气管上皮，并且已表明这些压缩力增强了培养物中这些细胞的促炎和促纤维形成介质的释放。重复发作的累加效应被认为会诱导气道重塑和气道壁间充质细胞的胶原沉积，从而导致哮喘期间出现的气道特征改变和不良特征。 我们开发了一种装置，能够对培养物中的上皮细胞施加压力，这种压力被认为是肺上皮在体内气道狭窄期间所经历的，并且具有提供指定压力振荡的新能力，我们相信这种能力更准确地模拟了急性哮喘发作期间传递到气道上皮的力。 为了表征这些效应，正常人支气管上皮 (NHLB) 细胞将单次或多次暴露于 4 小时的静态或振荡压力，并检测培养基中的转化生长因子-2、内皮素 1 和 2 以及纤连蛋白。 这些蛋白质的基因表达也将被表征。 然后将 NHLB 细胞暴露于前面描述的正常人肺成纤维细胞 (NHLF) 存在的条件下，以表征压缩诱导的细胞损伤期间的上皮-间质关系。 将评估胶原蛋白（I、III 和 V）、腱蛋白和纤连蛋白的基因表达，并利用多光子激光扫描显微镜来量化培养物中 NHLF 细胞的胶原蛋白沉积。 这项研究将使我们能够检查压缩诱导的细胞损伤对支气管上皮的影响，并将深入了解哮喘相关损伤期间的上皮-间质关系及其在纤维化发展中的参与。 这些研究的最终目标是帮助开发药物干预措施，以阻止慢性哮喘期间气道重塑和纤维化的进展。