Matrix metalloproteinase 2 (gelatinase A) is related to migration of keratinocytes
Matrix metalloproteinase 2 (gelatinase A) is related to migration of keratinocytes
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DOI：
10.1006/excr.1999.4564
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发表时间：
1999-08-25
影响因子：
3.7
通讯作者：
Uitto, VJ
中科院分区：
文献类型：
--
作者：
Mäkelä, M;Larjava, H;Uitto, VJ
基质金属蛋白酶（MMP）在细胞迁移中的作用进行了研究，通过测量细胞生长，迁移，MMP-2和-9在口腔粘膜和皮肤角质形成细胞的合成MMP抑制剂的存在下培养的生产。MMP-2是这些细胞产生的主要明胶分解MMP，而MMP-9在低基础水平产生。因此，在肿瘤坏死因子α（TNF α）刺激的角质形成细胞中研究了抑制剂对MMP-9产生的影响。抑制MMP-2而非MMP-9产生的浓度的四环素类似物能够显著抑制粘膜和皮肤角质形成细胞的迁移。四环素类似物也抑制角质形成细胞的生长，没有发现其他抑制剂测试的效果。杂环碳酸酯衍生的化合物（LWs），抑制MMP-9，但不MMP-2的生产对细胞迁移没有影响。巴马司他是一种有效的MMP抑制剂，对MMP产生或细胞生长没有任何影响，但确实抑制角质形成细胞迁移。肿瘤生长因子β（TGF β）增加角质形成细胞迁移以及受伤细胞培养物中细胞相关和分泌的MMP-2产生。分泌的酶部分转化为活性形式。在该模型中，巴马司他完全阻断TGF β促进的角质形成细胞迁移。进入伤口的角质形成细胞的免疫染色显示，MMP-2定位在细胞外基质接触样结构中，对抗内源性产生的富含层粘连蛋白Ei的基质。MMP-9沿细胞膜分布，呈弥漫性沿着分布。利用原位杂交，我们观察到，在慢性发炎的人牙龈MMP-2的表达在上皮延伸到上皮下结缔组织，这些结果表明，MMP-2在上皮迁移中起着特定的作用，可能是通过分离的推进细胞从细胞周基质或通过激活其他MMP。(C)北京：科学出版社.
The role of matrix metalloproteinases (MMPs) in cell migration was studied by measuring cell growth, migration, and production of MMP-2 and -9 in oral mucosal and skin keratinocytes cultured in the presence of synthetic MMP inhibitors. MMP-2 was the major gelatinolytic MMP produced by these cells while MMP-9 was produced at a low basal level. Inhibitor effects on MMP-9 production were therefore studied in keratinocytes stimulated by tumor necrosis factor alpha (TNF alpha), Tetracycline analogues at concentrations that inhibited the production of MMP-2 but not MMP-9 were able to drastically inhibit migration of both mucosal and skin keratinocytes. Tetracycline analogues also inhibited keratinocyte growth, an effect not found for the other inhibitors tested. Heterocyclic carbonate-derived compounds (LWs) that inhibited MMP-9 but not MMP-2 production had no effect on cell migration. Batimastat, a potent MMP inhibitor, did not have any effect on MMP production or cell growth but did inhibit keratinocyte migration. Tumor growth factor beta (TGF beta) increased keratinocyte migration as well as both cell-associated and secreted MMP-2 production in wounded cell cultures. The secreted enzyme was partially converted into an active form. In this model batimastat totally blocked TGF beta-promoted keratinocyte migration. Immunostaining of keratinocytes advancing into the wound revealed that MMP-2 was localized in extracellular matrix contactlike structures against the endogenously produced laminin-Ei-rich matrix. MMP-9 was localized diffusely along the cell membranes. Using in situ hybridization we observed that in chronically inflamed human gingiva MMP-2 is expressed in epithelium extending into subepithelial connective tissue, These results suggest that MMP-2 plays a specific role in epithelial migration, possibly by detaching the advancing cells from the pericellular matrix or by activating other MMPs. (C) 1999 Academic Press.