Lung Endothelial Cell Phenotypes

肺内皮细胞表型

• 批准号: 7822683
• 负责人: Troy Stevens
• 金额: $ 1.62万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7822683
• 关键词: Lung; Endothelial; Cell; Phenotypes

While endothelium has historically been considered a homogeneous cell layer, there is an increasing appreciation that it exhibits a rich diversity in structure and function. Heterogeneity is apparent between endothelial cells in different organs, in endothelial cells along a single vascular segment within an organ and, indeed, between immediately adjacent cells. This Program Project Grant is founded on the hypothesis that endothelium lining the lung's extra-alveolar and alveolar blood vessels is phenotypically distinct, and that the unique behavior(s) of cells from these different vascular locations is necessary for them to fulfill their sitespecific function(s). We currently possess a limited understanding of how such heterogeneity is achieved to control site-specific vascular demands, particularly in the lung's microvascular compartment. A principal goal in this competitive renewal application is therefore to rigorously determine molecular mechanisms that allow lung microvascular endothelial cells to successfully control their capillary function. Our focus on the microvascular endothelial cell phenotype is based upon the relative paucity of information regarding the behavior of this cell type. We propose four inter-related projects examining different signal transduction cascades that control lung microvascular endothelial cell behavior, including permeability regulation (Stevens, Project 1 and Townsley, Project 4), apoptosis/necrosis (Gillespie, Project 2), and von Willebrand factor secretion (Wu, Project 3). These projects are highly interactive both conceptually and pragmatically. Toward this end, this Program Project Grant draws on emerging developments in different fields of study, and applies these developments to generate new information about how microvascular lung endothelial cells, in particular, respond to inflammation and how they repair following injury. Defining the mechanisms that underlie lung microvascular endothelial cell function will provide insight into the site-specific nature of pulmonary vascular disease, and allow us to ultimately develop rational pharmacological therapies to discretely intervene in the endothelial cell dysfunction that occurs in all known pulmonary vascular diseases.

虽然内皮细胞历来被认为是一层均匀的细胞层，但越来越多的人 赞赏它在结构和功能上表现出丰富的多样性。两者之间的异质性很明显 不同器官中的内皮细胞，沿着器官内单个血管段的内皮细胞， 事实上，在紧邻的细胞之间。本计划项目赠款是建立在假设的基础上的 肺泡外血管和肺泡血管内皮细胞的表型是不同的， 这些不同血管位置的细胞的独特行为(S)是它们履行其部位特异性所必需的 函数(S)。我们目前对这种异质性是如何实现的了解有限 控制特定部位的血管需求，特别是在肺的微血管间隔。主要目标 因此，在这种竞争性更新应用中，严格地确定允许 肺微血管内皮细胞成功控制其毛细血管功能。我们的关注点是 微血管内皮细胞表型的基础是相对缺乏的关于 此单元格类型的行为。我们提出了四个相互关联的项目来研究不同的信号转导 控制肺微血管内皮细胞行为的级联反应，包括通透性调节 (史蒂文斯，项目1和汤斯利，项目4)，细胞凋亡/坏死(吉莱斯皮，项目2)，以及冯·威勒布兰德 因子分泌(吴，项目3)。这些项目在概念和实践上都具有很强的互动性。 为此，该计划项目赠款利用了不同研究领域的新发展， 并应用这些发展来产生关于微血管肺内皮细胞如何 特别是，细胞对炎症以及损伤后的修复方式做出反应。定义机制 肺微血管内皮细胞功能的基础将提供对部位特异性的洞察力 肺血管疾病，并允许我们最终开发合理的药物疗法来 对所有已知肺血管疾病中发生的内皮细胞功能障碍进行离散干预。