Role of Lung MSC in Emphysema

肺间充质干细胞在肺气肿中的作用

基本信息

批准号：
8599945
负责人：
SUSAN M MAJKA
金额：
$ 51.87万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8599945
关键词：
ABCG2 gene Ablation Address Adult Affect Alveolar Apoptosis Architecture Blood Vessels Blood capillaries Cartilage Cell Death Cell Line Cell Proliferation Cell physiology Cells Chronic Obstructive Airway Disease Colony-forming units Communities Data Development Distal Engineering Epithelial Epithelium Fatty acid glycerol esters Functional disorder Future Gases Goals Histology Homeostasis Hypoxia In Vitro Investigation Knock-out Knowledge Ligands Lung Lung diseases Maintenance Measures Medical Mesenchymal Stem Cells Modeling Mus Myofibroblast National Heart, Lung, and Blood Institute Pathology Pathway interactions Patients Phenotype Play Process Protocols documentation Pulmonary Emphysema Reagent Reporter Resources Role Rosa Signal Pathway Signal Transduction Small Interfering RNA Smoking Stem cells Structure Superoxide Dismutase Surface System Tamoxifen Therapeutic Intervention Time Tissues Toxin United States Vascular Endothelium alveolar epithelium base bone capillary cell type effective therapy extracellular in vivo inhibitor/antagonist innovation insight interest member mortality mouse model novel oxidant stress promoter public health relevance pulmonary function regenerative stemness therapeutic target

项目摘要

DESCRIPTION (provided by applicant): The proposed studies will use innovative approaches to expand upon our knowledge of lung stem cells to broaden treatment paradigms for NHLBI-related lung diseases. We therefore hypothesize that the maintenance of lung MSC function by Wnt/¿-catenin signaling is necessary for pulmonary tissue homeostasis. We propose to examine lung MSC-dependent mechanisms of abnormal pulmonary architecture and function using novel mouse models both in vitro and in vivo. We will determine the mechanism by which adult lung MSCs contribute to pulmonary tissue architecture and function in vivo. In addition, we will determine the mechanism by which Wnt/¿-catenin signaling regulates lung MSCs function and affects tissue homeostasis using both in vitro and in vivo novel systems. These models will enable us to identify a cell type which may be suited as a therapeutic target. Additionally, these studies will generate important resources and reagents that will be of vast interest to both the scientific and medical communities.

描述（由适用提供）：拟议的研究将采用创新方法来扩展我们对肺部干细胞的了解，以扩大与NHLBI相关肺部疾病的治疗范例。因此，我们假设Wnt/� -Catenin信号对肺MSC功能的维持是肺组织稳态所必需的。我们建议使用新颖的小鼠模型在体外和体内检查异常肺结构的肺MSC依赖机制和功能。我们将确定成年肺MSC在体内有助于肺组织结构和功能的机制。此外，我们将确定Wnt/® -Catenin信号传导调节肺MSC功能的机制，并使用体外和体内新型系统都会影响组织稳态。这些模型将使我们能够识别可能适合于治疗靶标的细胞类型。此外，这些研究将产生重要的资源和试剂，这对科学和医学界都引起了人们的关注。