INTEGRIN AVB6--ROLE IN BRONCHIOLAR INJURY/REPAIR

终末细支气管壁是损伤的主要靶点。 许多新陈代谢激活的外源生物。人们对此知之甚少 这种急性损伤后的细支气管修复，但已知一种 修复失败导致慢性毛细支气管炎、毛细支气管炎 闭塞症或肿瘤。修复过程的许多方面是 整合素类药物：异二聚体、跨膜糖蛋白 参与细胞与细胞或细胞与基质的黏附。一种新的一夫一妻制，非 结构型αvβ6整合素，已在 发育期肺分支呼吸道上皮细胞表达上调 炎症时的肺泡和支气管。以往对急性胰腺炎的研究 损伤提示αvβ6整合素起关键作用。 在修复中，尤指在细胞增殖中。使用定义良好的模型 对于小鼠细支气管上皮损伤，将使用萘 以实验性方式诱导急性损伤，以检查以下具体情况 目的：1)确定诱发相同程度的萘的剂量 野生型成年小鼠和7日龄小鼠对Clara细胞的杀伤作用 和β6转基因敲除小鼠，2)定义了表达模式 细支气管上皮修复过程中αvβ6整合素的表达 成人和新生野生型Clara细胞急性毒性反应 3)比较成年野生型小鼠的修复模式和 β6基因敲除小鼠。

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.