1,25-Dihydroxyvitamin D3 regulates VEGF production through a vitamin D response element in the VEGF promoter

In previous studies we have demonstrated that the active form of vitamin D (1,25(OH)(2)D-3) increases vascular endothelial growth factor (VEGF) expression and release in vascular smooth muscle Cells (VSMC) it? vitro. However, the mechanism by which 1,25(OH)(2)D-3 increases VEGF production is Currently unknown. In this work, we demonstrated binding of vitamin D receptor to two response elements in the VEGF promoter. We performed promoter transactivation analysis and we observed that, in 293T cells, VEGF promoter was activated after vitamin D treatment. Using site-directed mutagenesis we have shown that both response elements are important for VEGF promoter activity. Therefore, the increase in VEGF expression and secretion induced by 1,25(OH)(2)D-3 in VSMC in vitro could be explained by direct binding of the vitamin D receptor, as a transcription factor, to VEGF Promoter. These results Could explain part of the beneficial effects of vitamin D treatment in renal patients by a possible VEGF-mediated improvement of the endothelial dysfunction. (C) 2008 Elsevier Ireland Ltd. All rights reserved.