Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium
Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium
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DOI：
10.1016/s0002-9440(10)64318-0
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发表时间：
2003-06-01
影响因子：
6
通讯作者：
Parks, WC
中科院分区：
文献类型：
--
作者：
McGuire, JK;Li, QL;Parks, WC
基质溶素（基质金属蛋白酶-7）在肺纤维化和其他与气道和肺泡损伤相关的疾病患者的肺中高度表达。尽管基质溶解素是上皮细胞关闭所必需的。在离体创伤中，其在修复中的作用机制尚不清楚。我们证明，基质溶解素介导脱落的E-钙粘蛋白胞外域从受伤的肺上皮细胞在体外和体内。在肺泡样上皮细胞中，转染活化的基质溶解素导致脱落的E-钙粘蛋白和加速细胞迁移。在体内，matrilysin与E-钙粘蛋白共同定位在迁移气管上皮的基底外侧表面，并且在野生型损伤组织中观察到的细胞-细胞连接的重组在matrilysin空白样品中不存在。E-钙粘蛋白胞外域脱落到博莱霉素损伤的野生型小鼠的支气管肺泡灌洗液中，但在基质溶解素小鼠中不脱落。这些发现确定E-钙粘蛋白作为基质溶解素的一种新底物，并表明脱落的E-钙粘蛋白胞外域是上皮修复所必需的。
Matrilysin (matrix metalloproteinase-7) is highly expressed in lungs of patients with pulmonary fibrosis and other conditions associated with airway and alveolar injury. Although matrilysin is required for closure of epithelial. wounds ex vivo, the mechanism of its action in repair is unknown. We demonstrate that matrilysin mediates shedding of E-cadherin ectodomain from injured lung epithelium both in vitro and in vivo. In alveolar-like epithelial cells, transfection of activated matrilysin resulted in shedding of E-cadherin and accelerated cell migration. In vivo, matrilysin co-localized with E-cadherin at the basolateral surfaces of migrating tracheal epithelium, and the reorganization of cell-cell junctions seen in wild-type injured tissue was absent in matrilysin-null samples. E-cadherin ectodomain was shed into the bronchoalveolar lavage fluid of bleomycin-injured wild-type mice, but was not shed in matrilysin-mill mice. These findings identify E-cadherin as a novel substrate for matrilysin and indicate that shedding of E-cadherin ectodomain is required for epithelial repair.