title: TGF-beta effects on airway smooth muscle cell proliferation, VEGF release and signal transduction pathways.
abstract: OBJECTIVE
  Airway smooth muscle (ASM) cell hyperplasia is a key feature of airway remodelling. Mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) are key components in signal transduction associated with cell proliferation; MAPK consists of the extracellular signal-regulated kinase (ERK), p38MAPK and c-Jun NH(2)-terminal kinase (JNK). The effect of transforming growth factor (TGF)-beta on the proliferation of ASM cells, the release of vascular endothelial growth factor (VEGF) by ASM cells and relevant signal transduction pathways were investigated.
  
  
  METHODS
  ASM cells were growth-arrested for 48 h then stimulated with platelet-derived growth factor (PDGF), TGF-beta and dexamethasone. ASM cells were also treated with specific inhibitors of MAPK (PD98059), PI3K (wortmannin) and JNK (SP600125). Cell proliferation and VEGF concentrations were measured.
  
  
  RESULTS
  TGF-beta neither augmented ASM cell proliferation nor showed a synergistic effect on PDGF-mediated ASM cell proliferation. Dexamethasone did not suppress ASM cell proliferation. VEGF release was augmented by TGF-beta stimulation in a time-dependent manner, and was further enhanced by co-stimulation with PDGF and TGF-beta. Dexamethasone suppressed VEGF release significantly. TGF-beta enhanced PI3K phosphorylation, while PDGF augmented both ERK and PI3K phosphorylation. Wortmannin inhibited both TGF-beta- and PDGF-stimulated VEGF release.
  
  
  CONCLUSIONS
  TGF-beta may facilitate airway remodelling by promoting VEGF release through the PI3K pathway, rather than via ASM cell proliferation.
authors.affiliation: Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joo Hwa
authors.initials: JH
authors.lastname: Shin
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Shim
authors.forename: Deok Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Shim
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000873:Anthracenes; D005419:Flavonoids; D005938:Glucocorticoids; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C432165:pyrazolanthrone; D003907:Dexamethasone; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin