1,25-dihydroxyvitamin D3 stimulates vascular endothelial growth factor release in aortic smooth muscle cells:: Role of p38 mitogen-activated protein kinase

Vitamin D-3 plays an important role in the regulation of mineral homeostasis, cell differentiation, and proliferation. However, the exact role of vitamin D-3 in vascular smooth muscle cells remains unclear. In the present study, we investigated whether vitamin D-3 induces vascular endothelial growth factor (VEGF) release in aortic smooth muscle A10 cells. 1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)VD3), an active form of vitamin D-3, stimulated the VEGF release while 24,25-dihydroxyvitamin D-3 (24,25(OH)(2)VD3), an inactive form of vitamin D-3, had little effect on the release. The stimulatory effect of 1,25(OH)(2)VD3 was dose dependent in the range between 10 pM and 10 nM. 1,25(OH)(2)VD3 induced the phosphorylation of p38 mitogen-activated protein (MAP) kinase but 24,25(OH)(2)VD3 did not. PD169316 and SB203580, specific inhibitors of p38 MAP kinase, significantly reduced the 1,25(OH)(2)VD3-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)(2)VD3-induced phosphorylation of p38 MAP kinase. These results strongly suggest that 1,25(OH)(2)VD3 stimulates the release of VEGF in aortic smooth muscle cells via p38 MAP kinase activation. (C) 2002 Elsevier Science.