title: Cutting edge: extracellular high mobility group box-1 protein is a proangiogenic cytokine.
abstract: The chromosomal high mobility group box-1 (HMGB1) protein acts as a proinflammatory cytokine when released in the extracellular environment by necrotic and inflammatory cells. In the present study, we show that HMGB1 exerts proangiogenic effects by inducing MAPK ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells of different origin. Accordingly, HMGB1 stimulates membrane ruffling and repair of a mechanically wounded endothelial cell monolayer and causes endothelial cell sprouting in a three-dimensional fibrin gel. In keeping with its in vitro properties, HMGB1 stimulates neovascularization when applied in vivo on the top of the chicken embryo chorioallantoic membrane whose blood vessels express the HMGB1 receptor for advanced glycation end products (RAGE). Accordingly, RAGE blockade by neutralizing Abs inhibits HMGB1-induced neovascularization in vivo and endothelial cell proliferation and membrane ruffling in vitro. Taken together, the data identify HMGB1/RAGE interaction as a potent proangiogenic stimulus.
authors.affiliation: Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brecia, Brescia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mitola
authors.forename: Mirella
authors.initials: M
authors.lastname: Belleri
authors.forename: Chiara
authors.initials: C
authors.lastname: Urbinati
authors.forename: Daniela
authors.initials: D
authors.lastname: Coltrini
authors.forename: Bianca
authors.initials: B
authors.lastname: Sparatore
authors.forename: Marco
authors.initials: M
authors.lastname: Pedrazzi
authors.forename: Edon
authors.initials: E
authors.lastname: Melloni
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
mesh_terms: D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D002633:Chemotaxis / Q000502:physiology; D002642:Chick Embryo; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D024243:HMGB1 Protein / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2