Role of Lung MSC in Emphysema

肺间充质干细胞在肺气肿中的作用

• 批准号: 8848878
• 负责人: SUSAN M MAJKA
• 金额: $ 47.37万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8848878
• 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; Endothelium; Engineering; Epithelial; Epithelium; Fatty acid glycerol esters; Future; Gases; Goals; Health; 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 Diseases; alveolar epithelium; base; bone; capillary; cell type; effective therapy; extracellular; in vivo; inhibitor/antagonist; innovation; insight; interest; member; microCT; mortality; mouse model; novel; oxidant stress; promoter; pulmonary function; regenerative; stemness; targeted treatment; therapeutic target

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（由申请人提供）：拟议的研究将使用创新方法来扩展我们对肺干细胞的了解，以拓宽NHLBI相关肺部疾病的治疗模式。因此，我们假设通过Wnt/β-catenin信号传导维持肺MSC功能对于肺组织稳态是必要的。我们建议使用新的小鼠模型在体外和体内研究肺间充质干细胞依赖性机制的异常肺结构和功能。我们将确定成年肺间充质干细胞在体内促进肺组织结构和功能的机制。此外，我们将确定Wnt/β-连环蛋白信号调节肺间充质干细胞功能和影响组织稳态的机制，使用体外和体内新系统。这些模型将使我们能够识别可能适合作为治疗靶点的细胞类型。此外，这些研究将产生重要的资源和试剂，这将是科学和医学界的巨大兴趣。