title: Extracellular matrix proteins are potent agonists of human smooth muscle cell migration.
abstract: OBJECTIVE
  Extracellular matrix proteins can stimulate smooth muscle cell (SMC) migration by three distinct mechanisms: chemokinesis (nondirected migration in the presence of soluble protein), chemotaxis (directed migration toward soluble protein), and haptotaxis (directed migration toward insoluble, substrate-bound protein). This study investigates the effects of four prevalent extracellular matrix proteins (collagen types I and IV, fibronectin, and laminin), and platelet-derived growth factor (PDGF) on haptotaxis, chemotaxis, and chemokinesis of human SMCs. The role of large guanosine triphosphate-binding proteins (G-proteins) in the signaling mediating these effects is also evaluated.
  
  
  METHODS
  Human saphenous vein SMCs were used in all migration studies. Chemokinesis, chemotaxis, and haptotaxis to each of the matrix proteins were measured and compared with PDGF through the use of a 48-well microchemotaxis chamber. The role of G-proteins in matrix-induced SMC migration was studied with the modulators of G-protein function, cholera and pertussis toxins.
  
  
  RESULTS
  For all matrix proteins the relative strength of the various stimuli for migration was haptotaxis > chemotaxis > chemokinesis (p < 0.05). For all three stimuli collagen I and IV produced the most significant migration followed by fibronectin > PDGF-AB > laminin (p < 0.05). Pertussis toxin completely inhibited chemotaxis and partially inhibited haptotaxis by laminin but did not affect migration by other matrix proteins, whereas cholera toxin abolished migration in response to all four matrix proteins.
  
  
  CONCLUSIONS
  Matrix proteins, with the exception of laminin, provide a more significant stimulus for SMC locomotion than does the prototypical agonist, PDGF-AB. Of the three mechanisms by which migration can be stimulated, haptotaxis elicits the most profound effect. The importance of G-proteins as second messengers for migration varies with each matrix protein and with the mechanism of stimulation.
authors.affiliation: Department of Surgery (Division of Surgery), Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Nelson
authors.forename: S
authors.initials: S
authors.lastname: Yamamura
authors.forename: K C
authors.initials: KC
authors.lastname: Kent
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D037342:Pertussis Toxin; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology; D012501:Saphenous Vein / Q000166:cytology; D015290:Second Messenger Systems / Q000502:physiology; D013268:Stimulation, Chemical; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D016326:Extracellular Matrix Proteins; D010982:Platelet-Derived Growth Factor; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins