5-Aza-2'-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells
5-Aza-2'-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells
复制标题
DOI：
10.1016/j.biopha.2007.07.015
复制
发表时间：
2008-03-01
影响因子：
7.5
通讯作者：
Jagodziniski, P. P.
中科院分区：
文献类型：
--
作者：
Miller-Kasprzak, E.;Jagodziniski, P. P.
血管内皮生长因子（VEGF）参与血管生成、生长和肿瘤细胞转移。VEGF表达为可变剪接变体，其表现出血管生成和抗血管生成特性。我们确定了5-氮杂-2 '-脱氧胞苷（5-dAzaC）DNA甲基转移酶（DNMTs）抑制剂对永生化人肺微血管内皮细胞（HLMEC）中血管生成和抗血管生成VEGF变体表达的影响。采用逆转录、实时定量PCR（RQ-PCR）和Western blot分析，我们确定5-dAzaC降低HLMEC中VEGF（121 a）和VEGF（165 a）血管生成以及VEGF（121 b）和VEGF（165 b）抗血管生成变体的表达。然而，这种DNMTs抑制剂显著增加HLMEC中VEGF（189 b）抗血管生成变体转录物和蛋白的表达。我们的研究结果表明，DNMTs活性可能对人肺微血管内皮细胞中血管生成和抗血管生成VEGF变体的表达产生影响。(c)2007年，Elsevier Masson SAS。All rights reserved.
Vascular endothelial growth factor (VEGF) is involved in angiogenesis, growth, and tumour cell metastasis. VEGF is expressed as alternative splice variants, which exhibit angiogenic and anti-angiogenic properties. We determined the effect of 5-Aza-2'-deoxycytidine (5-dAzaC) DNA methyltransferase (DNMTs) inhibitor on angiogenic and anti-angiogenic VEGF variants expression in immortalized human lung microvascular endothelial cells (HLMEC). Employing reverse transcription, real-time quantitative PCR (RQ-PCR), and Western blot analysis, we determined that 5-dAzaC decreased VEGF(121a) and VEGF(165a) angiogenic, and VEGF(121b) and VEGF(165b) anti-angiogenic variants expression in HLMEC. However, this DNMTs inhibitor significantly increases expression of VEGF(189b) anti-angiogenic variant transcript and protein in HLMEC. Our results suggest that the DNMTs activity may have an influence on the expression of angiogenic and anti-angiogenic VEGF variants in human lung microvascular endothelial cells. (c) 2007 Elsevier Masson SAS. All rights reserved.