DEVELOPMENT AND DIFFERENTIATION OF AIRWAY EPITHELIUM

目标是生成信息，以扩大我们对 细支气管上皮的围生期发育。这个目标 涉及我们对Clara细胞生物学的长期兴趣的追求 但包括最近这种兴趣的扩展到对 小导气管细胞组成的调节 包括我们最近展示的一种材料， 一日龄大鼠富细支气管膜组织即条件介质制作 对14日龄大鼠的Clara细胞有丝分裂作用。因此，我们将： 1)基于已经在大鼠身上进行的试验的研究，假体 肺的内源性物质，可能与全身激素相一致， 以刺激或抑制的方式调节Clara复制；2)测试 在临床相关的围产期扰动(高氧，低氧， 早产、营养不良)，以确定它们是否会改变体内的 细支气管上皮的发育，如果有的话，确定是否 “追赶”常态化发生，并调查负责的机制 用于正常化；3)对人类出生晚期、产前和早期的 Clara细胞内成分的出生后发育变化 纤毛细胞和纤毛细胞的数量和数量 这些呼吸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，因为大多数提议的 实验是基于我们开发和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是 对其他研究人员和临床医生有用，并将大大促进 临床上重要但知之甚少且研究甚少的领域 呼吸生物学。

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.