title: Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells.
abstract: 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.
authors: Department of Obstetrics and Gynecology, The First Hospital, Harbin Medical University, Harbin, China; Department of Obstetrics and Gynecology, LSUHSC-Shreveport, LA, USA.
authors: Weijie
authors: W
authors: Zhong
authors: Department of Obstetrics and Gynecology, LSUHSC-Shreveport, LA, USA.
authors: Baihan
authors: B
authors: Gu
authors: Department of Obstetrics and Gynecology, LSUHSC-Shreveport, LA, USA.
authors: Yang
authors: Y
authors: Gu
authors: Department of Obstetrics and Gynecology, LSUHSC-Shreveport, LA, USA.
authors: Lynn J
authors: LJ
authors: Groome
authors: Department of Obstetrics and Gynecology, The First Hospital, Harbin Medical University, Harbin, China. Electronic address: sjxsw2013@163.com.
authors: Jingxia
authors: J
authors: Sun
authors: Department of Obstetrics and Gynecology, LSUHSC-Shreveport, LA, USA. Electronic address: ywang1@lsuhsc.edu.
authors: Yuping
authors: Y
authors: Wang
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
chemical_list: D018167:Receptors, Calcitriol; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D013482:Superoxide Dismutase; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C018021:cobaltous chloride; D002117:Calcitriol
keywords: Angiogenic property; CuZn-SOD; Endothelial cells; Oxidative stress; VDR