Vascular endothelial growth factor increases release of gelatinase a and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro
Vascular endothelial growth factor increases release of gelatinase a and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cells in vitro
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DOI：
10.1006/mvre.1997.2056
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发表时间：
1998-01-01
影响因子：
3.1
通讯作者：
Charles, ST
中科院分区：
文献类型：
--
作者：
Lamoreaux, WJ;Fitzgerald, MEC;Charles, ST
本研究旨在探讨血管内皮生长因子(VEGF)对人真皮微血管内皮细胞增殖和释放基质金属蛋白酶(MMPs)及其组织抑制物(TIMPs)的影响。加入10 ng/ml或以上浓度的血管内皮生长因子可显著促进细胞增殖。在加入10 ng/mlVEGF的培养上清液中检测VEGF对培养上清液中特异性MMPs和TIMPs水平的影响。酶谱分析和Western印迹分析表明，经血管内皮细胞生长因子处理后，培养上清液中明胶酶A的水平升高。Western blotting检测到VEGF处理的和未处理的培养上清液中均有胶原酶的表达，但经VEGF处理后，胶原酶的表达水平并未显著升高。一种酶联免疫吸附试验证实，血管内皮生长因子治疗显着增加明胶酶A水平，但不显着增加胶原酶水平。Western印迹和ELISA数据显示，与未处理的培养细胞相比，经血管内皮生长因子处理后，TIMP-1和TIMP-2的水平显著降低。结果提示，血管内皮细胞生长因子可能通过以下途径调节内皮细胞来源的基质金属蛋白酶活性：(1)增加明胶酶A的丰度；(2)通过降低TIMP-2的丰度来抑制明胶酶A的活性；(3)通过降低TIMP-1的水平来抑制先前存在的胶原酶。这些作用可能有助于促进血管内皮细胞侵袭新领域的能力。(C)1998年学术出版社。
The present study was designed to determine the influences of vascular endothelial growth factor (VEGF) on cell proliferation and the release of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) from human dermal microvascular endothelial cells. Treatment of cultures with 10 ng/ml or more of VEGF significantly increased cell proliferation. The effect of VEGF treatment on the levels of specific MMPs and TIMPs in the media was subsequently examined in cultures that were treated with 10 ng/ml VEGF. Zymography and Western blot analyses demonstrated that gelatinase A levels in the media were increased by VEGF treatment. Collagenase was detected by Western blots in both VEGF-treated and untreated culture media, but the levels were not significantly increased by the VEGF treatment. An ELISA assay confirmed that VEGF treatment significantly increased gelatinase A levels but did not significantly increase collagenase levels. Western blot and ELISA data showed that VEGF treatment significantly decreased TIMP-1 and TIMP-2 levels compared to untreated cultures. The data suggest that VEGF may modulate endothelial cell-derived MMP activity by: (1) increasing the abundance of gelatinase A; (2) disinhibiting gelatinase A by decreasing the abundance of TIMP-2; and (3) disinhibiting preexisting collagenase by reducing levels of TIMP-1. These actions could contribute to the ability of VEGF to promote endothelial cell invasion of new territory. (C) 1998 Academic Press.