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: 8496866
• 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/8496866
• 关键词: 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; 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 repair; 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.

描述（由申请人提供）：该基金旨在研究中性粒细胞在迁移过程中与上皮细胞相互作用激活肺上皮细胞2-连环蛋白依赖性信号通路的机制，以及这些通路在上皮修复中的重要性。我们将确定触发上皮细胞2-连环蛋白激活的信号通路，包括E-钙粘蛋白被PMN弹性蛋白酶裂解。我们将确定2- catenin激活促进体外PMN迁移诱导的上皮损伤修复的机制，并使用基因靶向小鼠建立ALI小鼠模型。