Binding of matrilysin-1 to human epithelial cells promotes its activity
Binding of matrilysin-1 to human epithelial cells promotes its activity
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DOI：
10.1007/s00018-007-6415-5
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发表时间：
2007-03-01
影响因子：
8
通讯作者：
Emonard, H.
中科院分区：
文献类型：
--
作者：
Berton, A.;Selvais, C.;Emonard, H.
基质金属蛋白酶-7（MMP-7，matrilysin- 1）通过处理许多上皮细胞表面相关效应物来调节重要的生物学事件。我们解决了MMP-7与人上皮细胞的相互作用及其产生的活性。在人子宫内膜中，一种受控组织重塑的模型，proMMP-7在上皮细胞内弥漫性免疫定位，而MMP-7描绘了它们的整个质膜。子宫内膜外植体优先保留活性MMP-7，而不是proMMP-7。子宫内膜癌来源的石川细胞对MMP-7表现出高亲和力（K-D近似于2.5 nM）和能力（近似于260000个位点/细胞）。MMP-7结合减少提取膜甾醇或干扰硫酸乙酰肝素蛋白聚糖，并废除了金属蛋白酶组织抑制剂-2（TIMP-2）或合成MMP抑制剂。结合的MMP-7不仅对大分子底物保持完全活性，而且对TIMP-2具有抗性。我们的结论是MMP-7选择性靶向上皮细胞的质膜，通过赋予TIMP-2的抗性来促进其活性。
Matrix metalloproteinase-7 (MMP-7, matrilysin- 1) modulates crucial biological events by processing many epithelial cell surface-associated effectors. We addressed MMP-7 interaction with human epithelial cells and its resulting activity. In human endometrium, a model of controlled tissue remodeling, proMMP-7 was diffusely immunolocalized inside epithelial cells, whereas MMP-7 delineated their entire plasma membrane. Endometrial explants preferentially retained active MMP-7, but not proMMP-7. Endometrial epithelial cells and carcinoma cells from various tissues bound active MMP-7 Endometrial carcinoma-derived Ishikawa cells showed high affinity (K-D of similar to 2.5 nM) and capacity (similar to 260 000 sites per cell) for MMP-7. MMP-7 binding decreased by extracting membrane sterols or interfering with heparan sulfate proteoglycans, and was abrogated by tissue inhibitors of metalloproteinase-2 (TIMP-2) or synthetic MMP inhibitors. Bound MMP-7 not only remained fully active towards a macromolecular substrate but also became resistant to TIMP-2. We conclude that MMP-7-selective targeting to the plasma membrane of epithelial cells promotes its activity by conferring resistance to TIMP-2.