ROLE OF CAVOLIN-1 IN AIRWAY REMODELING

CAVOLIN-1 在气道重塑中的作用

• 批准号: 8168079
• 负责人: Claude Le Saux
• 金额: $ 16.43万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168079
• 关键词: Affect; Allergens; Asthma; Basement membrane; CAV1 gene; Caveolae; Chronic; Complex; Computer Retrieval of Information on Scientific Projects Database; Connective Tissue; Deposition; Development; Disease; Fibroblasts; Fibrosis; Funding; Genetic Transcription; Goals; Grant; Inflammatory; Institution; Interleukin-4; Mediating; Mus; Myofibroblast; Populations at Risk; Proteins; Research; Research Personnel; Resources; Role; Source; Testing; Transforming Growth Factor beta; Transforming Growth Factor beta Receptors; United States; United States National Institutes of Health; airway obstruction; airway remodeling; allergic response; caveolin 1; computerized data processing; cytokine; human TGFB1 protein; inflammatory marker; response

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. The objective of this study is to determine the role of caveolae in airway remodeling in asthma. This chronic inflammatory disease of the airways affects an estimated 15 million people in the United States and 100-150 million people worldwide. Among this population at risk, a subset of subjects will develop irreversible remodeling and airway obstruction. Airway remodeling is characterized by an abnormally large number of myofibroblasts in the subepithelial basement membrane associated with significantly increased deposition of connective tissue proteins leading to a thickening of the lamina reticularis. Interleukin 4 (IL-4), a Th2 cytokine important in the control of allergic response, has also been proposed as an effector influencing airway remodeling. We have recently demonstrated that IL-4 regulates the expression of caveolin-1 (cav-1). Cav-1, main structural and functional protein of caveolae, notably regulates transforming growth factor (TGF)-beta activity by dampening its transduction signal process initiated by the TGF-beta receptor complex. TGF-beta1 is a pivotal pro-fibrotic cytokine in asthma and fibrosis. Our goal, therefore, is to demonstrate that Th2 cytokines, and more specifically IL-4, mediate caveolae deficiency by regulating cav-1 gene transcription in fibroblasts resulting in enhanced TGF-beta responses in airway remodeling. We will: 1) Evaluate the hypothesis that the reduced expression of cav1 is associated with the expression of inflammatory markers, more specifically IL-4 and TGF-beta, and the development of airway remodeling in allergen challenged mice. 2) Investigate the hypothesis that among the Th2 cytokines expressed in asthma, IL-4 regulates caveolin-1 expression and caveolae formation; 3) To test the hypothesis that the reduced expression of caveolin-1 protein enhances TGF-beta effects.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究的目的是确定小窝在气道重塑哮喘中的作用。 这种气道的慢性炎症性疾病影响了约1500万人 美国和全球1亿人口。在有风险的人群中，一个子集 受试者将产生不可逆的重塑和气道阻塞。气道重塑是 以异常数量的肌纤维细胞为特征 与结缔组织蛋白沉积显着增加相关的膜 导致薄片网状的增厚。白介素4（IL-4），Th2细胞因子很重要 在控制过敏反应的过程中，还提出了影响气道的效应器 重塑。我们最近证明IL-4调节了小窝蛋白-1的表达 （CAV-1）。 Cav-1，Caveolae的主要结构和功能蛋白，特别是调节 通过抑制其转导信号过程，转化生长因子（TGF）-Beta活性 由TGF-β受体复合物引发。 TGF-BETA1是一种关键的促纤维纤维性细胞因子 哮喘和纤维化。因此，我们的目标是证明Th2细胞因子等 特别是IL-4，通过调节成纤维细胞中的CAV-1基因转录来介导小窝缺乏症 导致气道重塑中的TGF-β响应增强。我们将：1）评估 假设Cav1的表达降低与表达有关 炎症标记，更具体地说是IL-4和TGF-beta，以及气道的发展 过敏原挑战小鼠的重塑。 2）研究TH2中的假设 IL-4在哮喘中表达的细胞因子调节小窝蛋白-1表达和小窝形成。 3） 为了测试可爱素-1蛋白表达降低的假设增强了TGF-β 效果。