PLASTICITY OF ALVEOLAR EPITHELIAL PHENOTYPIC EXPRESSION

描述(改编自申请人的摘要)：牙槽 上皮由两种类型的细胞组成，这两种细胞都被认为是 对生命来说必不可少的。II型细胞产生表面活性物质，并在 牙槽修补术。I型细胞的细小胞质延伸覆盖更多 超过95%的肺泡表面，提供短暂的扩散 对正常气体交换至关重要的途径。尽管重要的是 建立和维持正常的肺泡上皮，目前知之甚少 关于控制肺泡上皮细胞和分子因素的研究 表型表达。在体内，II型细胞具有修复能力 损伤肺泡，获得至少I型细胞的一些特征 表型。从有限的体外研究中，有人提出 I型和II型细胞之间可以发生可逆的转分化。 尽管在生物学上很有趣，而且对发育和肺很重要 这一假设还没有得到严格的检验。《博大》 这项建议中概述的研究的长期目标是 确定类型的表型可塑性(可互换性)的程度 I型和II型细胞，并定义调节其 表型表达。其目标是执行细胞和分子 研究人员对肺泡上皮表型表达的研究 最近开发的改进的体外系统，额外的标志物 类型I和类型II的表型以及分离高纯度类型的方法 I型和II型细胞。使用这些新开发的方法，他们将测试 转分化可以发生的潜在假说 I型和II型细胞之间的双向。使用标记用于 当前可用的I型或II型表型，它们将 测定肺泡上皮细胞转分化的程度 表型发生并将识别细胞和分子机制 在体外调节表型表达。他们将使用高度提纯的 为研究这两种细胞的功能而准备的细胞 以确定新的表型特异性基因。计划在这里进行的实验 提案应确定转分化发生的程度， 确定负责调控的特定细胞和分子机制 肺泡上皮细胞表型表达，并勾画出最先检测 I型细胞的功能。

DESCRIPTION (Adapted from the applicant's abstract): The alveolar epithelium is comprised of two cell types, both of which are believed to be essential to life. Type II cells produce surfactant and function in alveolar repair. The thin cytoplasmic extensions of type I cells cover more than 95 percent of the alveolar surface, providing the short diffusion pathway critical for normal gas exchange. Despite the importance of establishing and maintaining a normal alveolar epithelium, little is known about the cellular and molecular factors which control alveolar epithelial phenotypic expression. In vivo, type II cells have the capacity to repair injured alveoli, acquiring at least some characteristics of the type I cell phenotype. From limited in vitro studies, it has been proposed that reversible transdifferentiation can occur between type I and type II cells. Albeit biologically intriguing and of importance to development and lung injury, this hypothesis has not been rigorously examined. The broad long-term objectives of the studies outlined in this proposal are to determine the extent of phenotypic plasticity (interconvertability) of type I and type II cells and to define the mechanisms that regulate their phenotypic expression. With the goal of performing cellular and molecular studies of alveolar epithelial phenotypic expression, the investigators have recently developed improved in vitro systems, additional markers for the type I and type II phenotypes, and methods of isolating highly purified type I and type II cells. Using these newly developed methods, they will test the underlying hypothesis that transdifferentiation can occur bi-directionally between type I and type II cells. With the markers for type I or type II phenotypes that are currently available, they will determine the extent to which transdifferentiation of alveolar epithelial phenotypes occurs and will identify cellular and molecular mechanisms regulating phenotypic expression in vitro. They will use highly purified preparations of cells both to study the functions of both types of cells and to identify new phenotype-specific genes. The experiments planned in this proposal should determine the extent to which transdifferentiation occurs, define specific cellular and molecular mechanisms responsible for regulating alveolar epithelial phenotypic expression, and delineate the first tested functions of type I cells.