PLASTICITY OF ALVEOLAR EPITHELIAL PHENOTYPIC EXPRESSION

描述（改编自申请人摘要）：肺泡 上皮由两种细胞类型组成，据信这两种细胞类型都是 对生命至关重要。 II型细胞产生表面活性剂， 牙槽修复 I型细胞的薄的胞质延伸覆盖更多的细胞， 超过95%的肺泡表面，提供短扩散 正常气体交换的关键通道。 尽管重要的是 建立和维持正常的肺泡上皮，知之甚少 关于控制肺泡上皮细胞的细胞和分子因子 表型表达 在体内，II型细胞具有修复能力， 受损的肺泡，获得至少一些I型细胞的特征 表型。 根据有限的体外研究，已经提出， 可逆的转分化可以发生在I型和II型细胞之间。 尽管它在生物学上很有趣，对发育和肺很重要， 然而，这一假设尚未得到严格的检验。 广大 本建议中概述的研究的长期目标是 确定类型的表型可塑性（互变性）的程度 I型和II型细胞，并定义调节其 表型表达 目的是进行细胞和分子 肺泡上皮细胞表型表达的研究，研究人员已经 最近开发的改进的体外系统，用于 I型和II型表型，以及分离高度纯化的I型和II型表型的方法， I型和II型细胞。 使用这些新开发的方法，他们将测试 转分化可以发生的基本假设 在I型和II型细胞之间双向。 用记号笔 目前可用的I型或II型表型，它们将 确定肺泡上皮细胞转分化的程度 表型发生，并将确定细胞和分子机制 在体外调节表型表达。 他们将使用高纯度的 制备细胞，以研究两种类型细胞的功能， 来鉴定新的表型特异性基因。 计划中的实验 建议应该确定转分化发生的程度， 定义负责调节的特定细胞和分子机制 肺泡上皮细胞表型表达，并描绘了第一个测试 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.