Role of matrilysin-mediated E-cadherin shedding in wound healing

基质溶素介导的 E-钙粘蛋白脱落在伤口愈合中的作用

• 批准号: 7220807
• 负责人: SUSANNA Kosamo
• 金额: $ 5.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220807
• 关键词: Adherens Junction; Alveolus; Bacteria; Biological Assay; Bleomycin; C-terminal; Cell Adhesion Molecules; Cells; Chemotactic Factors; Cleaved cell; Cultured Cells; Data; Dissociation; E-Cadherin; Epithelial; Epithelial Cells; Epithelium; In Vitro; Infectious Agent; Inflammation; Inflammatory; Inflammatory Response; Injury; Intercellular Junctions; Knockout Mice; Leukocytes; Liquid substance; Lung; Maps; Matrilysin; Matrix Metalloproteinases; Mediating; Mesenchymal; Modeling; Mus; Mutation; Phenotype; Physiological; Process; Production; Protein Overexpression; Proteins; Recruitment Activity; Resistance; Role; Series; Site; Surface; Testing; Tissues; Transgenic Mice; Work; Wound Healing; cell injury; epithelial to mesenchymal transition; in vivo; in vivo Model; injured; injured airway; migration; repaired; research study; response; response to injury; synthetic peptide; wound

DESCRIPTION (provided by applicant): Role of matrilysin-mediated E-cadherin shedding in wound healing. Tissue injury leads to proliferation, differentiation, and migration of epithelial cells. These processes involve the coordinated action of various proteins, including several matrix metalloproteinases (MMPs). Previous data from our lab demonstrated that matrilysin (MMP-7) is required for repair of wounds to the lung. Matrilysin is expressed on basolateral surfaces of migrating airway epithelial cells, and it mediates E- cadherin shedding during the re-epithelialization process. In the absence of matrilysin, E-cadherin is not shed from wound edge cells in response to injury, and airway wounds do not close. We will test the hypothesis that matrilysin shedding of E-cadherin promotes epithelial-to-mesenchymal transformation and re-epithelialialization in mouse lungs. Aim1 is to identify the matrilysin cleavage site in mouse E-cadherin and to develop a proteolytic-resistant E-cadherin construct in an epithelial cell culture model. Aim 2 is to analyze the effect of E-cadherin shedding in vivo by developing a transgenic mouse line expressing a proteolytic-resistant E-cadherin on an E-cadherin-null background. The experiments proposed here will determine the function of matrilysin-mediated E-cadherin shedding in wound repair.

描述（由申请方提供）：基质溶解素介导的E-钙粘蛋白脱落在伤口愈合中的作用。组织损伤导致上皮细胞的增殖、分化和迁移。这些过程涉及各种蛋白质的协调作用，包括几种基质金属蛋白酶（MMP）。来自我们实验室的先前数据表明，基质溶解素（MMP-7）是修复肺部伤口所必需的。基质溶素在迁移的气道上皮细胞的基底外侧表面上表达，并且其在再上皮化过程中介导E-钙粘蛋白脱落。在没有基质溶解素的情况下，E-钙粘蛋白不会响应于损伤而从伤口边缘细胞脱落，并且气道伤口不会闭合。我们将测试这一假设，即基质溶解素脱落的E-钙粘蛋白促进上皮间充质转化和再上皮化小鼠肺。目的1是鉴定小鼠E-钙粘蛋白中的基质溶解素裂解位点，并在上皮细胞培养模型中开发抗蛋白水解的E-钙粘蛋白构建体。目的2是通过在E-钙粘蛋白缺失背景下建立表达抗蛋白水解E-钙粘蛋白的转基因小鼠系，分析E-钙粘蛋白脱落的体内效应。本文提出的实验将确定基质溶解素介导的E-钙粘蛋白脱落在伤口修复中的功能。