INTEGRIN AVB6--ROLE IN BRONCHIOLAR INJURY/REPAIR

整合素 AVB6——在细支气管损伤/修复中的作用

• 批准号: 2522357
• 负责人: GREG W. LAWSON
• 金额: $ 3.28万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2522357
• 关键词: environmental toxicology; gene targeting; genetically modified animals; integrins; laboratory mouse; lung injury; naphthalenes; regeneration; respiratory epithelium

The terminal bronchiolar epithelium is a primary target of injury for many metabolically activated xenobiotics. Little is known about bronchiolar repair following such acute injury, but it is known that a failure to repair results in chronic bronchiolitis, bronchiolitis obliterans or neoplasia. Many aspects of the repair process are medicated by integrins: heterodimeric, transmembrane glycoproteins involve in cell-cell or cell-matrix adhesion. A novel monogamous, non- constitutive alpha v beta 6 integrin, has been identified within the epithelia of branching airways of developing lung and is upregulated in alveoli and bronchi during inflammation. Previous studies of acute injury suggest that the alpha v beta 6 integrin plays a critical role in repair, especially in cell proliferation. Using a well defined model of bronchiole epithelial injury injury in mice, naphthalene will be used to experimentally induce acute injury to examine the following specific aims: 1)Establish the dose of naphthalene that induces the same degree of Clara cell cytotoxicity in both wild type adult and 7 day old mice and beta 6 transgenic knockout mice, 2)Define the pattern of expression of the alpha v beta 6 integrin during bronchiolar epithelial repair following acute Clara cell toxicity in adult and neonatal wild type mice, and 3) Compare the pattern of repair in adult wild type mice with beta 6 knockout mice.

终末细支气管上皮是肺损伤的主要靶点。 许多代谢活化的异生物质。 知之甚少 急性损伤后的细支气管修复，但众所周知， 修复失败导致慢性细支气管炎，细支气管炎 闭塞性或瘤形成。 修复过程的许多方面都是 由整合素介导：异二聚体跨膜糖蛋白 参与细胞-细胞或细胞-基质粘附。 一夫一妻制，非- 组成型α v β 6整联蛋白，已经在 在发育中的肺的分支气道的上皮中， 肺泡和支气管。 既往研究急性 损伤表明α v β 6整联蛋白起关键作用 在修复中，尤其是在细胞增殖中。 使用定义良好的模型 在小鼠细支气管上皮损伤损伤中，将使用萘 实验性诱导急性损伤，以检查以下特定的 目的：1）确定萘对小鼠的致敏剂量 Clara细胞在野生型成年小鼠和7日龄小鼠中的细胞毒性 和β 6转基因敲除小鼠，2）定义表达模式 α v β 6整合素在细支气管上皮修复过程中的作用 在成年和新生野生型中发生急性Clara细胞毒性后 小鼠，以及3）将成年野生型小鼠的修复模式与 β 6基因敲除小鼠。