DEVELOPMENT AND DIFFERENTIATION OF AIRWAY EPITHELIUM

气道上皮的发育和分化

• 批准号: 3353527
• 负责人: GLORIA D MASSARO
• 金额: $ 15.29万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-15 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353527
• 关键词: bronchioles; cell differentiation; cell growth regulation; electron microscopy; histogenesis; human fetus tissue; human tissue; hyperoxia; hypoxia; laboratory rat; malnutrition; mature animal; mitogens; newborn animals; premature infant animal; premature infant human; respiratory epithelium; sex hormones; thyroid hormones; tissue /cell culture

The goal is to generate information that will enlarge our understanding of the perinatal development of the bronchiolar epithelium. This goal involves the pursuit of our long standing interest in Clara cell biology but includes the more recent expansion of this interest to studies of the regulation of the cellular composition of small conducting airways including our recent demonstration of a material present in bronchiolar-rich tissue of one day old rats that conditions medium to make it mitogenic in vitro for Clara cells of 14 day old rats. Thus we will: 1) based on studies already preformed test in rats the hpothesis that substances endogenous to lungs, perhaps in concert with systemic hormones, modulate Clara replication in a stimulatory or inhibitory manner; 2) test in rats clinically relevant perinatal perturbations (hyperoxia, hypoxia, prematurity, undernutrition) to determine if they modify the in vivo development of the bronchiolar epithelium, and, if they do, determine if "catch-up" normalization occurs, and investigate the mechanisms responsible for the normalization; 3) quantitate in humans the late prenatal and early postnatal developmental changes of the intracellular components of Clara cells and ciliated cells in small conducting airways and quantitate the developmental changes in the epithelial cell population of these airways. We think we can achieve these goals because most of the proposed experiments are based on extensive preliminary data we have developed and because we are our consultants have had extensive experience with most of the procedures and systems we propose to use. We believe our data will be useful to other investigators and clinicians and will substantially advance a clinically important but poorly understood and little studied area of respiratory biology.

我们的目标是产生信息，扩大我们对 细支气管上皮的围产期发育。 这一目标 涉及到我们对克拉拉细胞生物学的长期兴趣 但包括最近这种兴趣对研究的扩展 调节小传导气道的细胞组成 包括我们最近展示的一种材料， 一日龄大鼠的富含细支气管的组织， 体外对14日龄大鼠Clara细胞有丝分裂作用。 因此，我们将： 1)基于已经在大鼠中进行的试验的研究， 肺内源性物质，可能与全身激素一致， 以刺激或抑制的方式调节Clara复制; 2）测试 在大鼠中，临床相关的围产期扰动（高氧，缺氧， 早产，营养不良），以确定它们是否改变了体内 细支气管上皮细胞的发育，并且，如果他们这样做，确定是否 “赶考”常态化发生，并追究责任机制 3）在人类中定量晚期产前和早期 克拉拉细胞内成分的生后发育变化 细胞和纤毛细胞在小的传导气道，并定量 这些气道上皮细胞群的发育变化。 我们认为我们可以实现这些目标，因为大多数建议 实验是基于我们已经开发的大量初步数据， 因为我们是我们的顾问，对大多数 我们建议使用的程序和系统。 我们相信我们的数据将 对其他研究人员和临床医生有用， 一个临床上重要的，但知之甚少，研究很少的领域， 呼吸生物学