Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells

作者：Zhong Weijie; Gu Baihan; Gu Yang; Groome Lynn J; Sun Jingxia^*; Wang Yuping

来源：Journal of Steroid Biochemistry and Molecular Biology, 2014, 140: 56-62.

DOI：10.1016/j.jsbmb.2013.11.017

• VDR
• Angiogenic property
• CuZn-SOD
• Oxidative stress
• Endothelial cells

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)(2)D-3 stimulation and oxidative stress challenge in endothelial cells. We found that 1,25(OH)(2)D-3 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)(2)D-3 induced increased VEGF and KDR expression and prevented 1,25(OH)(2)D-3 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)(2)D-3 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.

• 出版日期2014-3
• 单位哈尔滨医科大学