title: Angiopoietin-1 mediates the proangiogenic activity of the bone morphogenic protein antagonist Drm.
abstract: Recent observations have shown that Drm, a member the Dan family of bone morphogenic protein (BMP) antagonists, induces endothelial cell (EC) sprouting in vitro and angiogenesis in vivo by interacting with signaling EC receptors in a BMP-independent manner. Here, recombinant Drm (rDrm) up-regulates angiopoientin-1 (Ang-1) expression in EC without affecting Ang-2 and Tie-2 receptor expression. Ang-1 up-regulation is mediated by the activation of the transcription factor NF-kappaB. Specific inhibition of Ang-1 activity by anti-Ang-1 antibodies, soluble Tie-2 receptor, or Ang-1 siRNA transfection significantly reduced the rDrm-mediated sprouting of EC in three-dimensional fibrin and type I collagen gels. In addition, Ang-1 antagonists inhibited the angiogenic activity exerted by rDrm in the chick embryo chorioallantoic membrane. Taken together, the data indicate that the proangiogenic activity of Drm is mediated by the activation of an Ang-1-dependent autocrine loop of stimulation in EC.
authors.affiliation: Department of Biomedical Sciences and Biotechnology, Unit of General Pathology and Immunology, University of Brescia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mitola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Moroni
authors.forename: Cosetta
authors.initials: C
authors.lastname: Ravelli
authors.forename: German
authors.initials: G
authors.lastname: Andres
authors.forename: Mirella
authors.initials: M
authors.lastname: Belleri
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
mesh_terms: D042501:Angiogenic Proteins; D042683:Angiopoietin-1 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019898:Autocrine Communication; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002642:Chick Embryo; D016207:Cytokines; D042783:Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic; D042787:Receptor, TIE-2; D015854:Up-Regulation / Q000235:genetics
chemical_list: D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D042787:Receptor, TIE-2; C113178:Grem1 protein, mouse; C486399:GREM1 protein, human