Activities of the matrix metalloproteinase stromelysin-2 (MMP-10) in matrix degradation and keratinocyte organization in wounded skin
Activities of the matrix metalloproteinase stromelysin-2 (MMP-10) in matrix degradation and keratinocyte organization in wounded skin
复制标题
DOI：
10.1091/mbc.e04-02-0109
复制
发表时间：
2004-12-01
影响因子：
3.3
通讯作者：
Werner, S
中科院分区：
文献类型：
--
作者：
Krampert, M;Bloch, W;Werner, S
基质金属蛋白酶基质溶素-2在皮肤伤口的上皮舌的角质形成细胞中表达，表明在角质形成细胞迁移中的作用。在这里，我们表明，基质分解素-2增强培养的角质形成细胞的迁移。为了深入了解基质分解素-2在上皮修复中的体内活性，我们产生了在角质形成细胞中表达组成型活性基质分解素-2突变体的转基因小鼠。这些动物的皮肤结构没有改变，皮肤伤口的愈合率正常。然而，在组织学上，我们发现伤口上皮的组织异常。迁移性表皮尖端的角质形成细胞散在分布于大部分切片中，且表达水平较高，新基质沉积减少。特别是，层粘连蛋白-5在伤口部位的染色模式被改变。这可能是由于层粘连蛋白-5被基质溶解素-2蛋白水解加工，因为在体外观察到层粘连蛋白-5被这种酶降解。角质形成细胞的不适当的基质接触伴随着β 1-整合素和磷酸化粘着斑激酶的异常定位，以及伤口角质形成细胞的凋亡增加。这些结果表明，基质分解素-2的表达水平的严格调节是有限的基质降解在伤口部位，从而控制角质形成细胞迁移所必需的。
The matrix metalloproteinase stromelysin-2 is expressed in keratinocytes of the epithelial tongue of skin wounds, suggesting a role in keratinocyte migration. Here, we show that stromelysin-2 enhances migration of cultured keratinocytes. To gain insight into the in vivo activities of stromelysin-2 in epithelial repair, we generated transgenic mice expressing a constitutively active stromelysin-2 mutant in keratinocytes. These animals had no alterations in skin architecture, and the healing rate of skin wounds was normal. Histologically, however, we found abnormalities in the organization of the wound epithelium. Keratinocytes at the migrating epidermal tip were scattered in most sections of mice with high expression level, and there was a reduced deposition of new matrix. In particular, the staining pattern of laminin-5 at the wound site was altered. This may be due to proteolytic processing of laminin-5 by stromelysin-2, because degradation of laminin-5 by this enzyme was observed in vitro. The inappropriate matrix contact of keratinocytes was accompanied by aberrant localization of beta1-integrins and phosphorylated focal adhesion kinase, as well as by increased apoptosis of wound keratinocytes. These results suggest that a tightly regulated expression level of stromelysin-2 is required for limited matrix degradation at the wound site, thereby controlling keratinocyte migration.