1,25-Dihydroxyvitamin D3 regulates VEGF production through a vitamin D response element in the VEGF promoter
1,25-Dihydroxyvitamin D3 regulates VEGF production through a vitamin D response element in the VEGF promoter
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DOI：
10.1016/j.atherosclerosis.2008.08.020
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发表时间：
2009-05-01
期刊：
影响因子：
5.3
通讯作者：
Valdivielso, Jose M.
中科院分区：
文献类型：
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作者：
Cardus, Anna;Panizo, Sara;Valdivielso, Jose M.
在以前的研究中，我们已经证明活性形式的维生素D(1，25(OH)(2)D-3)增加血管内皮生长因子(VEGF)在血管平滑肌细胞(VSMC)的表达和释放。体外培养。然而，1，25(OH)(2)D-3促进血管内皮生长因子产生的机制目前尚不清楚。在这项工作中，我们证明了维生素D受体与血管内皮生长因子启动子中的两个反应元件结合。我们进行了启动子反式激活分析，我们观察到，在293T细胞中，经维生素D处理后，VEGF启动子被激活。利用定点突变，我们已经证明了这两个反应元件对血管内皮生长因子启动子的活性都很重要。因此，1，25(OH)(2)D-3诱导VSMC表达和分泌血管内皮生长因子的作用可以通过维生素D受体作为转录因子直接与血管内皮生长因子启动子结合来解释。这些结果可以部分解释维生素D治疗对肾脏患者的有益效果，可能是通过血管内皮生长因子介导的改善内皮功能障碍。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
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.