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

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.