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、控制和紊乱进行多学科研究。该提案的目的是研究在发育和出生后生活以及在健康和疾病状态下肺实质形成和稳定所涉及的一些机制。我们所说的稳定是指综合的物理、化学和生物过程，这些过程发展并维持肺泡结构处于最佳状态，以利于肺气体交换。正如我们过去的研究一样，我们强调对肺泡上皮发育、肺表面活性物质系统的功能以及导致感染和炎症的肺泡疾病过程的研究。 拟议的三个相互关联的项目的总体目标是： 项目1：表面活性蛋白质的结构和功能。目的：研究肺表面活性物质蛋白，特别是SP-D的结构与其调节肺泡免疫环境功能的关系。 项目2：CEACAM6在肺泡组织中的表达及作用。探讨癌胚抗原-6在肺泡天然免疫防御、肺表面活性物质功能及肺上皮细胞对急性肺损伤反应中的作用。 项目3：肺泡上皮细胞命运：图谱和调控。研究肺泡上皮细胞在发育和再生过程中的谱系，阐明在肺泡上皮细胞分化过程中重要的新的调节分子。 这些研究的总体目的是加深我们对肺实质稳定性的基础过程的理解，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 the 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. By stabilization we mean the integrated physiochemical and biological processes that develop and maintain alveolar architecture in an optimal state for pulmonary gas exchange. As in our past studies we emphasize investigations of alveolar epithelial development, functions of the lung surfactant system, and alveolar disease processes leading to infection and inflammation. The broad goals of the three inter-related projects proposed are: Project 1: Structure and function of surfactant proteins. To study the relationship between the structure of the surfactant proteins, specifically SP-D, and their functions in regulating the immune milieu of the alveolus. Project 2: Expression and role of CEACAM6 in the alveolus. To investigate the role of carcinoembryonic antigen-6 in alveolar innate immune defense, surfactant function, and epithelial response to acute lung injury. Project 3: Alveolar epithelial cell fates: mapping and regulation. To study alveolar epithelial cell lineages during development and regeneration and to elucidate novel regulatory molecules important to the process of alveolar epithelial differentiation. 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.