Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis
Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis
复制标题
1-磷酸鞘氨醇通过转录因子 ZNF580 诱导人内皮细胞 VEGF 和 MMP-2 的产生：对血管生成的新见解
DOI：
10.1016/j.bbrc.2010.04.019
复制
发表时间：
2010-05-07
影响因子：
3.1
通讯作者：
Zhang, Wen-Cheng
中科院分区：
文献类型：
--
作者：
Sun, Hui-Yan;Wei, Shu-Ping;Zhang, Wen-Cheng
鞘氨醇-1-磷酸（S1 P）诱导的内皮细胞迁移和增殖是血管生成的关键。C2 H2-锌指（ZNF）蛋白在改变基因表达和调节血管生成中起重要作用。本研究的目的是探讨一个新的人类C2 H2-锌指基因ZNF 580（基因ID：51157）是否参与SIP刺激的内皮细胞迁移和增殖。我们的研究表明EAhy 926内皮细胞表达S1 P1、S1 P3和S1 P5受体。此外，S1 P上调ZNF 580 mRNA和蛋白水平的浓度和时间依赖性的方式。SB 203580是p38丝裂原活化蛋白激酶（p38 MAPK）通路的特异性抑制剂，可阻断SW诱导的ZNF 580上调。此外，ZNF 580在EAhy 926细胞中的过表达/低表达可导致基质金属蛋白酶-2（MMP-2）和血管内皮生长因子（VEGF）表达的增强/降低以及EAhy 926内皮细胞的迁移和增殖。这些结果阐明了ZNF 580在内皮细胞迁移和增殖过程中发挥的重要作用，为调节血管生成的新方法提供了基础。(C)2010年爱思唯尔公司All rights reserved.
Sphingosine-1-phosphate (S1P)-induced migration and proliferation of endothelial cells are critical for angiogenesis. C2H2-zinc finger (ZNF) proteins usually play an essential role in altering gene expression and regulating the angiogenesis. The aim of this study is to investigate whether a novel human C2H2-zinc finger gene ZNF580 (Gene ID: 51157) is involved in the migration and proliferation of endothelial cells stimulated by SIP. Our study shows that EAhy926 endothelial cells express S1P1, S1P3 and S1P5 receptors. Furthermore, S1P upregulates both ZNF580 mRNA and protein levels in a concentration- and time-dependent manner. SB203580, the specific inhibitor of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, blocks the SW-induced upregulation of ZNF580. Moreover, overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression as well as the migration and proliferation of EAhy926 endothelial cells. These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis. (C) 2010 Elsevier Inc. All rights reserved.