1,25-dihydroxyvitamin D3 stimulates vascular endothelial growth factor release in aortic smooth muscle cells: role of p38 mitogen-activated protein kinase.
Vitamin D3 plays an important role in the regulation of mineral homeostasis, cell differentiation, and proliferation. However, the exact role of vitamin D3 in vascular smooth muscle cells remains unclear. In the present study, we investigated whether vitamin D3 induces vascular endothelial growth factor (VEGF) release in aortic smooth muscle A10 cells. 1,25-Dihydroxyvitamin D3 (1,25(OH)2VD3), an active form of vitamin D3, stimulated the VEGF release while 24,25-dihydroxyvitamin D3 (24,25(OH)2VD3), an inactive form of vitamin D3, had little effect on the release. The stimulatory effect of 1,25(OH)2VD3 was dose dependent in the range between 10 pM and 10 nM. 1,25(OH)2VD3 induced the phosphorylation of p38 mitogen-activated protein (MAP) kinase but 24,25(OH)2VD3 did not. PD169316 and SB203580, specific inhibitors of p38 MAP kinase, significantly reduced the 1,25(OH)2VD3-stimulated release of VEGF. On the contrary, SB202474, a negative control for p38 MAP kinase inhibitor, had little effect on the VEGF release. PD169316 attenuated the 1,25(OH)2VD3-induced phosphorylation of p38 MAP kinase. These results strongly suggest that 1,25(OH)2VD3 stimulates the release of VEGF in aortic smooth muscle cells via p38 MAP kinase activation.
Yamamoto
Takuji
T
Department of Pharmacology, Gifu University School of Medicine, Gifu, 500-8705, Japan.
Kozawa
Osamu
O
Tanabe
Kumiko
K
Akamatsu
Shigeru
S
Matsuno
Hiroyuki
H
Dohi
Shuji
S
Hirose
Hajime
H
Uematsu
Toshihiko
T
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D016228:Endothelial Growth Factors / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
D016228:Endothelial Growth Factors; D007093:Imidazoles; D008222:Lymphokines; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015650:24,25-Dihydroxyvitamin D 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002117:Calcitriol; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole; C093642:SB 203580