Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor.
Endothelial cells (EC) under stress release paracrine mediators that facilitate accumulation of vascular smooth muscle cells (VSCM) at sites of vascular injury. We found that medium conditioned by serum-starved EC increase proliferation and migration of VSCM in vitro. Fractionation of the conditioned medium followed by mass spectral analysis identified one bioactive component as vitamin D-binding protein (DBP). DBP induced both proliferation and migration of VSMC in vitro in association with increased phosphorylation of ERK 1/2. PD 98059, a biochemical inhibitor of ERK 1/2, abrogated these proliferative and migratory responses in VSMC. DBP is an important carrier for the vitamin-D sterols, 25-hydroxyvitamin-D, and 1alpha,25-dihydroxyvitamin-D. Both sterols inhibited the activity of DBP on VSMC, suggesting that vitamin D binding sites are important for initiating the activities of DBP on VSMC. Release of DBP at sites of endothelial injury represents a novel pathway favoring accumulation of VSMC at sites of vascular injury.
Raymond
Marc-André
MA
Research Centre CHUM, University of Montreal, 1560 Sherbrooke East, Montreal, Que., Canada H2L 4M1.
Désormeaux
Anik
A
Labelle
Andrée
A
Soulez
Mathilde
M
Soulez
Gilles
G
Langelier
Yves
Y
Pshezhetsky
Alexey V
AV
Hébert
Marie-Josée
MJ
D000595:Amino Acid Sequence; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006133:Growth Substances / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D019899:Paracrine Communication; D010766:Phosphorylation; D012995:Solubility; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D006133:Growth Substances; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3