Role of Beta-catenin in Epithelial Repair in Acute Lung Injury

β-连环蛋白在急性肺损伤上皮修复中的作用

• 批准号: 7953459
• 负责人: Rachel Lynne Zemans
• 金额: $ 12.52万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953459
• 关键词: Acute; Acute Lung Injury; Air Sacs; Alveolar; Area; Binding; Cadherins; Cell Death; Cell Line; Clinical; Complication; Critical Illness; Data; Disease; E-Cadherin; Elastases; Epithelial; Epithelial Cells; Epithelium; Expenditure; Figs - dietary; Gene Targeting; Genetic Transcription; Goals; Grant; Health Care Costs; In Vitro; Inflammatory; Injury; Leukocyte Elastase; Lung; Mechanical ventilation; Mediating; Membrane; Modeling; Morbidity - disease rate; Mus; Pathway interactions; Patients; Peptide Hydrolases; Permeability; Phase; Play; Population; Proliferating; Proteins; Recovery; Research; Research Personnel; Role; Severities; Signal Pathway; Signal Transduction; Speed; Supportive care; Tight Junctions; alveolar epithelium; alveolar type II cell; antimicrobial; beta catenin; design; injured; lung injury; mortality; neutrophil; novel therapeutics; public health relevance; receptor; repaired; response

DESCRIPTION (provided by applicant): This grant seeks to investigate the mechanisms by which PMN interactions with epithelial cells during transmigration activate 2-catenin-dependent signaling pathways in lung epithelial cells and the importance of these pathways in epithelial repair. We will determine the signaling pathways that trigger epithelial 2-catenin activation including E-cadherin cleavage by PMN elastase. We will determine the mechanisms by which 2- catenin activation promotes repair of epithelial injury induced by PMN transmigration in vitro and in murine models of ALI using gene-targeted mice. PUBLIC HEALTH RELEVANCE: Acute Lung Injury (ALI) is a frequent complication in critically ill patients that is responsible for significant morbidity, mortality, and the expenditure of > $50 billion annually in health care costs. To date, aside from lung protective mechanical ventilation strategies and supportive care, there are no specific therapies for ALI and mortality rates remain unacceptably high (20-50%). Recovery from ALI is dependent on repair of the cells that line the air sacs of the lung (epithelial cells). We have discovered that 2-catenin, an intracellular protein, promotes repair of these lining cells. We propose to study how this beneficial effect is exerted with the goal of identifying specific targets for therapies to speed recovery from this devastating disorder.

描述（由申请人提供）：该赠款旨在研究肺部上皮细胞中PMN与上皮细胞相互作用与上皮细胞相互作用的机制，以及这些途径在上皮修复中的重要性。我们将确定触发上皮2-catenin激活的信号通路，包括PMN弹性酶的E-钙粘蛋白裂解。我们将确定2- catenin激活促进PMN透射在体外诱导的上皮损伤的机制，并使用靶向基因的小鼠在ALI的鼠模型中诱导的上皮损伤。 公共卫生相关性：急性肺损伤（ALI）是重症患者的常见并发症，负责大量发病率，死亡率和每年的卫生保健费用大于500亿美元。迄今为止，除了肺部保护性机械通气策略和支持性护理外，ALI和死亡率还没有特定的疗法（20-50％）。从ALI中恢复的取决于修复肺部气囊（上皮细胞）的细胞。我们发现2-catenin是一种细胞内蛋白，可促进这些内膜细胞的修复。我们建议研究如何发挥这种有益作用，目的是确定疗法的特定靶标，以加快这种毁灭性疾病的恢复。