title: Lack of ERK activation and cell migration in FGF-2-deficient endothelial cells.
abstract: The formation of blood capillaries from preexisting vessels (angiogenesis) and vascular remodeling secondary to atherosclerosis or vessel injury are characterized by endothelial cell migration and proliferation. Numerous growth factors control these cell functions. Basic fibroblast growth factor (FGF-2), a potent angiogenesis inducer, stimulates endothelial cell proliferation, migration, and proteinase production in vitro and in vivo. However, mice genetically deficient in FGF-2 have no apparent vascular defects. We have observed that endothelial cell migration in response to mechanical damage in vitro is accompanied by activation of the extracellular signal-regulated kinase (ERK) pathway, which can be blocked by neutralizing anti-FGF-2 antibodies. Endothelial cells from mice that are genetically deficient in FGF-2 neither migrate nor activate ERK in response to mechanical wounding. Addition of exogenous FGF-2 restores a normal cell response, which shows that impaired migration results from the genetic deficiency of this growth factor. Injury-induced ERK activation in endothelial cells occurs only at the edge of the wound. In addition, FGF-2-induced ERK activation mediates endothelial cell migration in response to wounding without a significant effect on proliferation. These data show that FGF-2 is a key regulator of endothelial cell migration during wound repair.
authors.affiliation: The Seymour Cohn Cardiovascular Surgical Research Laboratory, Division of Cardiothoracic Surgery, New York University School of Medicine, New York, New York, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pintucci
authors.forename: David
authors.initials: D
authors.lastname: Moscatelli
authors.forename: Fiorella
authors.initials: F
authors.lastname: Saponara
authors.forename: Peter R
authors.initials: PR
authors.lastname: Biernacki
authors.forename: F Gregory
authors.initials: FG
authors.lastname: Baumann
authors.forename: Costas
authors.initials: C
authors.lastname: Bizekis
authors.forename: Aubrey C
authors.initials: AC
authors.lastname: Galloway
authors.forename: Claudio
authors.initials: C
authors.lastname: Basilico
authors.forename: Paolo
authors.initials: P
authors.lastname: Mignatti
mesh_terms: D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000494:pharmacology; D017353:Gene Deletion; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D013314:Stress, Mechanical
chemical_list: D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases