Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells.
Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells.
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DOI：
10.1016/j.jsbmb.2013.11.017
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发表时间：
2014-03
影响因子：
4.1
通讯作者：
Wang, Yuping
中科院分区：
文献类型：
--
作者：
Zhong, Weijie;Gu, Baihan;Gu, Yang;Groome, Lynn J.;Sun, Jingxia;Wang, Yuping
与维生素D缺乏相关的内皮功能障碍与许多慢性血管疾病有关。维生素D通过与靶细胞和器官上的受体维生素D受体（VDR）结合而发挥其生物活性。在本研究中，我们研究了VDR在内皮细胞对1,25(OH)2D3刺激和氧化应激挑战的反应中的作用。我们发现1,25(OH)2D3不仅诱导了VDR表达的剂量依赖性和时间依赖性增加，还诱导了血管内皮生长因子（VEGF）及其受体（Flt-1和KDR）以及抗氧化剂cuzn -超氧化物歧化酶（CuZn-SOD）在内皮细胞中的表达上调。我们证明，通过VDR siRNA抑制VDR可阻断1,25(OH)2D3诱导VEGF和KDR表达增加，并阻止1,25(OH)2D3诱导的内皮细胞增殖/迁移。利用模拟缺氧的CoCl2，我们发现缺氧/氧化应激不仅降低了内皮细胞中CuZn-SOD的表达，还下调了VDR的表达，这可以通过在培养中添加1,25(OH)2D3来预防。这些结果提示内皮细胞可诱导VDR表达，氧化应激可下调内皮细胞VDR表达。我们认为充足的维生素D水平和适当的VDR表达是内皮细胞血管生成和氧化防御功能的基础。
Endothelial dysfunction associated with vitamin D deficiency has been linked to many chronic vascular diseases. Vitamin D elicits its bioactive actions by binding to its receptor, vitamin D receptor (VDR), on target cells and organs. In the present study, we investigated the role of VDR in response to 1,25(OH)2D3 stimulation and oxidative stress challenge in endothelial cells. We found that 1,25(OH)2D3 not only induced a dose- and time-dependent increase in VDR expression, but also induced up-regulation of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and KDR), as well as antioxidant CuZn-superoxide dismutase (CuZn-SOD) expression in endothelial cells. We demonstrated that inhibition of VDR by VDR siRNA blocked 1,25(OH)2D3 induced increased VEGF and KDR expression and prevented 1,25(OH)2D3 induced endothelial proliferation/migration. Using CoCl2, a hypoxic mimicking agent, we found that hypoxia/oxidative stress not only reduced CuZn-SOD expression, but also down-regulated VDR expression in endothelial cells, which could be prevented by addition of 1,25(OH)2D3 in culture. These findings are important indicating that VDR expression is inducible in endothelial cells and oxidative stress down-regulates VDR expression in endothelial cells. We conclude that sufficient vitamin D levels and proper VDR expression are fundamental for angiogenic and oxidative defense function in endothelial cells.
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影响因子：
3
作者：
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