title: The role of phospholipase C and phosphatidylinositol 3-kinase in vascular smooth muscle cell migration and proliferation.
abstract: BACKGROUND
  Vascular smooth muscle cell (SMC) proliferation and migration both contribute to the formation of intimal hyperplasia. Phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3-K) are ubiquitous signaling proteins that mediate multiple cellular events. In this study, we investigate the role of PLC and PI3-K in platelet-derived growth factor (PDGF) and extracellular matrix protein (ECM) induced SMC proliferation and migration.
  
  
  METHODS
  Proliferation of human saphenous vein SMC was assessed by (3)H-thymidine incorporation. SMC migration was evaluated using a microchemotaxis chamber. U-73122 was used as a general inhibitor for PLC, and D609 and ET-18-OCH3, respectively, were used to block the isotypes of PLC, phosphatidylcholine- (PC-), and phosphatidylinositol- (PI-) specific PLC. PI3-K activity was inhibited using two selective inhibitors, LY-294002 and wortmannin.
  
  
  RESULTS
  PDGF and Type 1 collagen (CN-I) stimulated SMC proliferation, whereas PDGF and four distinct extracellular matrix proteins CN-I, Type 4 collagen (CN-IV), fibronectin (FN), and laminin (LN) stimulated SMC migration. Both isotypes of PLC as well as PI3-K were necessary for PDGF- and CN-I-induced proliferation. Signaling for migration, however, was more specific. Of the various signaling proteins studied, only PI-PLC was necessary for PDGF-induced SMC migration. Conversely, PI3-K was the only signaling protein necessary for SMC migration in response to ECM proteins.
  
  
  CONCLUSIONS
  The signaling pathways necessary for PDGF- and CN-I-induced SMC proliferation involve both isotypes of PLC as well as PI3-K. The signaling pathways used by growth factors and ECM to stimulate SMC migration are more selective. Understanding the intracellular signaling pathways required for SMC proliferation and migration may allow the development of tools to selectively block intimal hyperplasia.
authors.affiliation: Department of Surgery, Division of Vascular Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, 525 East 68th Street, Payson 707, New York, NY 1002, USA. bol2001@med.cornell.edu
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itoh
authors.forename: Otway
authors.initials: O
authors.lastname: Louie
authors.forename: Kenji
authors.initials: K
authors.lastname: Kubota
authors.forename: K Craig
authors.initials: KC
authors.lastname: Kent
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010738:Type C Phospholipases