Matrilysin expression and function in airway epithelium
Matrilysin expression and function in airway epithelium
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DOI：
10.1172/jci1516
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发表时间：
1998-10-01
影响因子：
15.9
通讯作者：
Parks, WC
中科院分区：
文献类型：
--
作者：
Dunsmore, SE;Saarialho-Kere, UK;Parks, WC
我们报道了基质溶解素，一种基质金属蛋白酶，在正常肺的支气管周围腺体和传导气道的上皮中组成性表达。基质溶素的表达增加，在气道上皮细胞和肺泡II型细胞在囊性纤维化诱导。其他金属蛋白酶（胶原酶-1，基质溶解素-1，92-kD明胶酶）不产生正常或受伤的肺上皮。这些观察结果表明，基质溶解素功能损伤介导的反应的肺。事实上，在受伤的人和小鼠气管中迁移的气道上皮细胞中，基质溶解素的表达增加。在人类组织中，异羟肟酸抑制剂使上皮迁移减少> 80%，在小鼠组织中，基质溶素缺失小鼠气管中的上皮再形成基本上被阻断。体内观察和细胞培养研究表明，基质溶解素由肺上皮细胞腔分泌，但在激活后或在伤口上迁移时，一些基质溶解素被释放。基质溶素在传导气道中的组成性产生、其在损伤后的上调、其由肺泡上皮的诱导以及其向管腔和基质隔室的释放表明，这种金属蛋白酶在完整和损伤的肺中具有多种功能，其中之一是促进上皮再形成。
We report that matrilysin, a matrix metalloproteinase, is constitutively expressed in the epithelium of peribronchial glands and conducting airways in normal lung. Matrilysin expression was increased in airway epithelial cells and was induced in alveolar type II cells in cystic fibrosis. Other metalloproteinases (collagenase-1, stromelysin-1, and 92-kD gelatinase) were not produced by normal or injured lung epithelium. These observations suggest that matrilysin functions in injury-mediated responses of the lung. Indeed, matrilysin expression was increased in migrating airway epithelial cells in wounded human and mouse trachea. In human tissue, epithelial migration was reduced by > 80% by a hydroxamate inhibitor, and in mouse tissue, reepithelialization in trachea from matrilysin-null mice was essentially blocked. In vivo observations and cell culture studies demonstrated that matrilysin was secreted lumenally by lung epithelium, but upon activation or while migrating over wounds, some matrilysin was released basally. The constitutive production of matrilysin in conducting airways, its upregulation after injury, its induction by alveolar epithelium, and its release into both lumenal and matrix compartments suggest that this metalloproteinase serves multiple functions in intact and injured lung, one of which is to facilitate reepithelialization.