A secreted MMP is required for reepithelialization during wound healing.
A secreted MMP is required for reepithelialization during wound healing.
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DOI：
10.1091/mbc.e11-09-0745
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发表时间：
2012-03
影响因子：
3.3
通讯作者：
Page-McCaw A
中科院分区：
文献类型：
--
作者：
Stevens LJ;Page-McCaw A
基质金属蛋白酶（MMPs）在伤口愈合中的作用一直难以分析，因为在24个小鼠MMPs中存在冗余。果蝇只有两个mmmp，每个MMP都是表皮伤口愈合所必需的。Mmp1促进基底膜组装、细胞迁移和ERK信号传导，其水平与愈合速度相关。基质金属蛋白酶（MMPs）是在伤口部位高度表达的细胞外蛋白酶。然而，在哺乳动物模型中，由于24种哺乳动物MMPs的高度冗余，MMPs在体内再上皮化过程中的确切功能一直难以捉摸。因此，我们利用黑腹果蝇的基因组只编码两种mmp——一种分泌型（Mmp1）和一种膜锚定型（Mmp2）——来研究分泌型mmp在体内的功能和调控。在没有冗余的情况下，我们发现果蝇分泌的MMP，即Mmp1，在表皮中通过重塑基底膜、促进细胞伸长和肌动蛋白细胞骨架重组、激活细胞外信号调节的激酶信号传导来促进再上皮化。此外，我们报道了jun n -末端激酶（JNK）途径在损伤后上调Mmp1的表达，但Mmp1在未损伤的表皮中独立于JNK途径表达。当JNK通路被异位激活以过度表达Mmp1时，愈合速度以Mmp1依赖的方式加快。在JNK通路的控制下，Mmp1的一个主要功能是促进基底膜修复，这反过来可能允许细胞迁移和连续组织的恢复。
The role of matrix metalloproteinases (MMPs) in wound healing has been difficult to analyze because of redundancy among the 24 mouse MMPs. Drosophila has only two MMPs, and each MMP is required for epidermal wound healing. Mmp1 promotes basement membrane assembly, cell migration, and ERK signaling, and its levels correlate with the rate of healing. Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaster, whose genome encodes only two MMPs—one secreted type (Mmp1) and one membrane-anchored type (Mmp2)—to study the function and regulation of the secreted class of MMPs in vivo. In the absence of redundancy, we found that the Drosophila secreted MMP, Mmp1, is required in the epidermis to facilitate reepithelialization by remodeling the basement membrane, promoting cell elongation and actin cytoskeletal reorganization, and activating extracellular signal-regulated kinase signaling. In addition, we report that the jun N-terminal kinase (JNK) pathway upregulates Mmp1 expression after wounding, but that Mmp1 is expressed independent of the JNK pathway in unwounded epidermis. When the JNK pathway is ectopically activated to overexpress Mmp1, the rate of healing is accelerated in an Mmp1-dependent manner. A primary function of Mmp1, under the control of the JNK pathway, is to promote basement membrane repair, which in turn may permit cell migration and the restoration of a continuous tissue.