Miller-Kasprzak E, Jagodziński P P
Department of Biochemistry and Molecular Biology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
Biomed Pharmacother. 2008 Mar;62(3):158-63. doi: 10.1016/j.biopha.2007.07.015. Epub 2007 Aug 23.
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.
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。