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5-氮杂-2'-脱氧胞苷增加人肺微血管内皮细胞中抗血管生成血管内皮生长因子189b变体的表达。

5-Aza-2'-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells.

作者信息

Miller-Kasprzak E, Jagodziński P P

机构信息

Department of Biochemistry and Molecular Biology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.

出版信息

Biomed Pharmacother. 2008 Mar;62(3):158-63. doi: 10.1016/j.biopha.2007.07.015. Epub 2007 Aug 23.

Abstract

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.

摘要

血管内皮生长因子(VEGF)参与血管生成、生长及肿瘤细胞转移。VEGF以可变剪接变体的形式表达,这些变体具有促血管生成和抗血管生成特性。我们测定了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)中促血管生成和抗血管生成VEGF变体表达的影响。通过逆转录、实时定量PCR(RQ-PCR)及蛋白质印迹分析,我们确定5-dAzaC降低了HLMEC中促血管生成的VEGF(121a)和VEGF(165a)以及抗血管生成的VEGF(121b)和VEGF(165b)变体的表达。然而,这种DNMTs抑制剂显著增加了HLMEC中抗血管生成变体VEGF(189b)的转录本和蛋白表达。我们的结果表明,DNMTs活性可能对人肺微血管内皮细胞中促血管生成和抗血管生成VEGF变体的表达有影响。

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