title: Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor.
abstract: 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.
authors.affiliation: Research Centre CHUM, University of Montreal, 1560 Sherbrooke East, Montreal, Que., Canada H2L 4M1.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Raymond
authors.forename: Anik
authors.initials: A
authors.lastname: Désormeaux
authors.forename: Andrée
authors.initials: A
authors.lastname: Labelle
authors.forename: Mathilde
authors.initials: M
authors.lastname: Soulez
authors.forename: Gilles
authors.initials: G
authors.lastname: Soulez
authors.forename: Yves
authors.initials: Y
authors.lastname: Langelier
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Pshezhetsky
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Hébert
mesh_terms: 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*
chemical_list: 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