Development and Control of Pulmonary Alveolar Stability

描述（由申请人提供）： 本申请建议继续对肺实质的发育、控制和疾病进行多学科研究。本提案的目的是研究在发育和出生后生活期间以及在健康和疾病状态下涉及肺实质形成和稳定的一些机制。在我们过去的研究中，我们建议强调肺分支和生长，肺泡上皮细胞的发育和功能，肺表面活性物质系统的功能，肺泡疾病过程导致炎症和纤维化的调查。 提出的四个相互关联的项目的广泛目标是：项目1：表面活性剂蛋白的结构和功能：研究表面活性剂脱辅基蛋白的结构和它们在调节表面活性剂稳态和肺泡免疫环境中的功能之间的关系。项目二：腱生蛋白与肺损伤：研究腱生蛋白在急性肺损伤和肺纤维化发生发展中的作用。 项目三：肺分支形态发生的分子机制：研究肺发育过程中的上皮-间充质相互作用，特别强调成纤维细胞生长因子和Sonic Hedgehog信号传导和相互作用。 项目四：肺泡上皮细胞表型的调控：阐明发育过程中肺泡上皮细胞表型表达调控的机制。 这些研究的总体目的是加深我们对肺实质稳定性基础过程的理解，并为与肺泡稳定性、生长、成熟和损伤后修复障碍相关的肺部疾病提供新的概念和治疗方法。

DESCRIPTION (provided by applicant): This application proposes to continue multidisciplinary studies of development, control and disorders of the pulmonary parenchyma. The objectives of this proposal are to examine some of the mechanisms involved in the formation and stabilization of the pulmonary parenchyma, during development and post-natal life, and in states of health and disease. As in our past studies, we propose to emphasize investigations of lung branching and growth, alveolar epithelial cell development and functions, functions of the lung surfactant system, and alveolar disease processes leading to inflammation and fibrosis. The broad goals of the four inter-related projects proposed are: Project 1: Structure and function of surfactant proteins: To study the relationship between the structure of the surfactant apoproteins and their functions in regulating surfactant homeostasis and the immune milieu of the alveolus. Project 2: Tenascins and lung injury: To study the role of the tenascin proteins in acute lung injury and the development of pulmonary fibrosis. Project 3: Molecular mechanisms of lung branching morpho-genesis: To study epithelial-mesenchymal interactions during lung development with a specific emphasis on fibroblast growth factor and sonic hedgehog signaling and interactions. Project 4: Regulation of alveolar epithelial cell phenotype: To elucidate mechanisms responsible for the regulation of alveolar epithelial cell phenotypic expression during development. The overall purpose of these studies is to deepen our understanding of the processes underlying lung parenchymal stability and to contribute to new concepts and treatments for lung diseases associated with disorders of alveolar stability, growth, maturation, and repair after injury.