Modulation by the steroid/thyroid hormone superfamily of TGF-β-stimulated VEGF release from vascular smooth muscle cells

Abstract

We previously reported that transforming growth factor-β (TGF-β) stimulates the release of vascular endothelial growth factor (VEGF) from aortic smooth muscle A10 cells via activation of p38 mitogen-activated protein (MAP) kinase. In the present study, we investigated whether nuclear hormone receptor superfamily members affect TGF-β-stimulated VEGF release from A10 cells. Retinoic acid or 1,25-dihydroxyvitamin D3 enhanced TGF-β-induced VEGF release in a concentration-dependent manner, whereas dexamethasone or corticosterone suppressed TGF-β-induced VEGF release. 1,25-Dihydroxyvitamin D3 and TGF-β stimulated phosphorylation of p38 MAP kinase in an additive manner. SB203580, an inhibitor of p38 MAP kinase, decreased the VEGF release induced by TGF-β or 1,25-dihydroxyvitamin D3. However, retinoic acid, dexamethasone, or corticosterone did not affect phosphorylation of p38 MAP kinase. These results indicate that retinoic acid, 1,25-dihydroxyvitamin D3, and glucocorticoids affect TGF-β-stimulated VEGF release from aortic smooth muscle cells. The stimulatory effect of 1,25-dihydroxyvitamin D3 occurs, in part, via modification of TGF-β-induced activation of p38 MAP kinase. © 2006 Wiley-Liss, Inc.