CELLULAR INTERACTIONS IN PULMONARY OXYGEN TOXICITY

肺氧中毒中的细胞相互作用

• 批准号: 6725377
• 负责人: ANBUKILI CHETTY
• 金额: $ 12.83万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-18 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725377
• 关键词: binding proteins; cell cell interaction; cell proliferation; collagen; cytotoxicity; fibroblasts; growth factor receptors; hyperoxia; insulinlike growth factor; laboratory rat; lung development; lung injury; respiratory epithelium; retinoate; tissue /cell culture

DESCRIPTION (provided by applicant): Cellular Interactions in Pulmonary Oxygen Toxicity in Developing Lung: Candidates background: The candidate has been interested in the pathophysiology of pulmonary diseases in children since her fellowship at Columbia University, NY. Since then she has worked in the field of Asthma and interstitial lung diseases in children. With her experience reinforced with her desire to learn basic research, she was awarded NIH training Grant Fellowship at Case Western Reserve University, Cleveland. Expertise in in vitro co-cultures, cell-cell interaction, cell migration, and hyperoxic exposure of neonatal rat pups was developed. Her stay at New England Medical Center further cultivated this in developing lung. Career goals and objectives: Her goal is to pursue a career as an independent Scientific Investigator, she remains deeply committed to Basic Science research as a way to better understand and treat chronic lung diseases in children. The transition from supervised to independent investigator will require additional years of structured training. Environment: The environment has been excellent with readily available critical review of experimental design and results, and assistance with learning the many new technical procedures required for developing expertise in this area of cell-cell interaction in hyperoxic lung injury. The Advisory Committee consists of authorities in Lung Development and Hyperoxic lung injury in New England Medical Center, Harvard University, Boston Medical Center, and NIDDK, National Institute of Health. Hypothesis: Interaction between Insulin-like growth factor-I (IGF-I) and IGF- I receptor (IGF-IR) is an important regulatory mechanism in hyperoxic lung injury in developing lung. Specific aims: 1. The onset of hyperoxic lung injury in developing lugs is associated with an increase in the expression of IGF-1 in epithelial cells and an increase in the expression of IGF-IR in fibroblasts. 2. IGF-I and IGF-IR interaction regulates epithelial cell- fibroblast communication in hyperoxic lung injury. Induction of fibroblast proliferation and collagen synthesis will be used as evidence of cell-cell interaction using the in vitro and in vivo experiments, and it will be tested by blocking the interaction by various strategies. 3. Retinoic acid decreases the proliferative effect of IGF-I through its action on IGF binding proteins. This mentored work will provide extensive education and technical experience in Molecular Biology and the development of a model of hyperoxic lung injury.

描述（由申请人提供）： 肺发育中肺氧毒性的细胞相互作用： 候选人背景：候选人对以下领域感兴趣 自她在该校获得奖学金以来，儿童肺部疾病的病理生理学研究 纽约哥伦比亚大学。 从那时起，她一直致力于哮喘领域的工作 儿童间质性肺疾病。 随着她的经验得到加强 她渴望学习基础研究，因此获得了 NIH 培训补助金 克利夫兰凯斯西储大学奖学金。 专业知识在 体外共培养、细胞间相互作用、细胞迁移和高氧 开发了新生大鼠幼崽的暴露方法。 她在新英格兰医疗中心的住宿 中心进一步培育了这一点，以发展肺部。 职业目标和 目标：她的目标是追求作为独立科学工作者的职业生涯 作为一名研究员，她仍然坚定地致力于基础科学研究 更好地了解和治疗儿童慢性肺部疾病。 这 从受监督到独立调查员的过渡将需要额外的 多年的结构化培训。 环境： 环境已经 非常出色，可以随时对实验设计进行严格审查，并且 结果，并帮助学习许多新技术程序 需要发展细胞间相互作用领域的专业知识 高氧性肺损伤。 咨询委员会由肺科权威人士组成 哈佛大学新英格兰医学中心的发育和高氧肺损伤 大学、波士顿医学中心和 NIDDK、国立卫生研究院。 假设：胰岛素样生长因子-I (IGF-I) 和 IGF- 之间的相互作用 I受体（IGF-IR）是高氧肺的重要调节机制 发育中的肺损伤。 具体目标： 1. 肺高氧的发生 发育中的耳损伤与表达增加有关 上皮细胞中的 IGF-1 以及 IGF-IR 表达的增加 成纤维细胞。 2. IGF-I和IGF-IR相互作用调节上皮细胞- 高氧性肺损伤中的成纤维细胞通讯。 成纤维细胞的诱导 增殖和胶原蛋白合成将作为细胞间存在的证据 使用体外和体内实验进行相互作用，并将对其进行测试 通过各种策略来阻止交互。 3.视黄酸减少 IGF-I 通过其对 IGF 结合蛋白的作用而发挥增殖作用。 这项指导工作将提供广泛的教育和技术经验 分子生物学和高氧肺损伤模型的开发。