title: [Role of MAPK in the migration of human coronary artery smooth muscle cell into three-dimensional fibrin gel].
abstract: OBJECTIVE
  To investigate the role of MAPK in the migration of human coronary artery smooth muscle cells(HCASMC ) into three-dimensional fibrin gels.
  
  
  METHODS
  HCASMC were primarily cultured. HCASMC migration was measured with a phase-contrast microscope in the presence or absence of PD98059, SB203580, and SP600125, the inhibitors of ERK, p38, and JNK, respectively. Phosphorylation of ERK, p38 and JNK were analyzed by Western blotting in the presence or absence of PD98059, SB203580 or SP600125.
  
  
  RESULTS
  HCASMC that migrated into the three-dimensional fibrin gel exhibited a characteristic elongated spindle-shaped appearance and formed vessel-like structure. The number of migrated HCASMC increased with incubation time and concentration of fibrinogen in the range between 0.8 g/L and 6.4 g/L. Western blot showed that fibrin induced phosphorylation of ERK, p38 and JNK time dependently and PD98059, SB203580 and SP600125 could inhibit their activation, respectively. Migration of HCASMC into the fibrin gels was inhibited by SP600125 20 micromol/L and SB203580 10 micromol/L, respectively. Furthermore, inhibition of SP600125 20 micromol/L had a more profound effect. PD98059 50 ,mol/L, however, failed to influence migration of HCASMC. Hence, migration of HCASMC into the fibrin gels is JNK- and p38-dependent, but not ERK-dependent.
  
  
  CONCLUSIONS
  Fibrin gel induces HCASMC migration into itself by activation of JNK and p38, but not ERK, which may play an important role in pathogenesis of atherothrombosis and restenosis.
authors.affiliation: Cardiovascular Research Institute of PLA, Department of Cardiology, General Hospital of Shenyang Military Region, China. hanyal@mail.sy.ln.cn
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Han
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Qi
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Ming
authors.initials: M
authors.lastname: Liang
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Chen
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D002465:Cell Movement; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; C432165:pyrazolanthrone; D005337:Fibrin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one