title: Thrombospondin 1, fibronectin, and vitronectin are differentially dependent upon RAS, ERK1/2, and p38 for induction of vascular smooth muscle cell chemotaxis.
abstract: BACKGROUND
  Thrombospondin 1 (TSP-1), fibronectin (Fn), and vitronectin (Vn) promote vascular smooth muscle cell (VSMC) chemotaxis through a variety of second messenger systems, including Ras, ERK1/2, and p38.
  
  
  OBJECTIVE
  Ras, ERK1/2, and p38 differentially affect TSP-1-, Fn-, and Vn-induced VSMC chemotaxis.
  
  
  METHODS
  Bovine VSMCs were transfected with Ras N17 or treated with the following inhibitors: a farnesyl protein transferase (FPT) inhibitor, PD098059 (ERK1/2 inhibitor), or SB202190 (p38 inhibitor). Thrombospondin 1, Fn, and Vn were used as chemoattractants. Results were analyzed by analysis of variance (ANOVA) with post hoc testing (P < .05).
  
  
  RESULTS
  Ras N17 transfection or FPT inhibitor treatment inhibited TSP-1-, Fn-, and Vn-induced chemotaxis. PD098059 or SB202190 resulted in more inhibition of VSMC migration to TSP-1 than to Fn or Vn.
  
  
  CONCLUSIONS
  Ras appears equally relevant in the signal transduction pathways of TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. Thrombospondin 1-induced migration is more dependent upon ERK1/2 and p38 than Fn- or Vn-included migration.
authors.affiliation: Yale University School of Medicine Section of Vascular Surgery, New Haven, CT, USA.
authors.forename: Alliric I
authors.initials: AI
authors.lastname: Willis
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sadowitz
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fuse
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Maier
authors.forename: Tae S
authors.initials: TS
authors.lastname: Lee
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Wang
authors.forename: George P
authors.initials: GP
authors.lastname: Tuszynski
authors.forename: Bauer E
authors.initials: BE
authors.lastname: Sumpio
authors.forename: Vivian
authors.initials: V
authors.lastname: Gahtan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism*; D014162:Transfection; D019096:Vitronectin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D047428:Protein Kinase Inhibitors; D019700:Thrombospondin 1; D019096:Vitronectin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins