title: Vascular smooth muscle cell migration induced by domains of thrombospondin-1 is differentially regulated.
abstract: BACKGROUND
  Thrombospondin-1 (TSP-1) stimulates vascular smooth muscle cell (VSMC) migration via defined intracellular signaling pathways. The aim of this study was to examine the signaling pathways whereby TSP-1 folded domains (amino-terminal [NH(2)], procollagen homology [PCH], all 3 type 1 repeats [3TSR], and a single recombinant protein containing the 3rd type 2 repeat, the type 3 repeats, and the carboxyl-terminal [E3T3C1]) induce VSMC migration.
  
  
  METHODS
  Quiescent VSMCs were pretreated with serum-free media or inhibitors: PP2 (c-Src), LY294002 (phosphatidylinositol 3-kinase), FPT (Ras), Y27632 (Rho kinase), SB202190 (p38 kinase), and PD98059 (extracellular signal-regulated kinase). Migration induced by serum-free media, TSP-1, NH(2), PCH, 3TSR, and E3T3C1 was assessed using a modified Boyden chamber.
  
  
  RESULTS
  TSP-1, NH(2), 3TSR, and E3T3C1 induced VSMC chemotaxis (P < .05), but PCH did not (P > .05). PP2, FPT, SB202190, and PD98059 attenuated chemotaxis stimulated by TSP-1, NH(2), 3TSR, and E3T3C1 (P < .05). LY294002 inhibited TSP-1-induced and E3T3C1-induced (P < .05) but not NH(2)-induced or 3TSR-induced (P > .05) chemotaxis. Y27632 inhibited NH(2)-induced, 3TSR-induced, and E3T3C1-induced (P < .05) but not TSP-1-induced (P > .05) induced chemotaxis.
  
  
  CONCLUSIONS
  TSP-1 folded domains are differentially dependent on intracellular signaling pathways to induce migration.
authors: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA.
authors: Keri A
authors: KA
authors: Seymour
authors: Benjamin
authors: B
authors: Sadowitz
authors: Jeffrey J
authors: JJ
authors: Stein
authors: Jack
authors: J
authors: Lawler
authors: Kristopher G
authors: KG
authors: Maier
authors: Vivian
authors: V
authors: Gahtan
mesh_terms: D000577:Amides / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D063065:Organophosphonates / Q000494:pharmacology; D017510:Protein Folding; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D019700:Thrombospondin 1 / Q000502:physiology*
chemical_list: C436083:2-(2-oxo-2-((3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy)aminoethyl)phosphonic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester sodium; C412373:AG 1879; D000577:Amides; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D009025:Morpholines; D063065:Organophosphonates; D011725:Pyridines; D011743:Pyrimidines; D019700:Thrombospondin 1; C108830:Y 27632; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one