title: The suppression effects of thalidomide on human lung fibroblasts: cell proliferation, vascular endothelial growth factor release, and collagen production.
abstract: BACKGROUND
  Expression of transforming growth factor (TGF)-β1 and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production.
  
  
  METHODS
  Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β1-induced VEGF, and signal pathway were investigated.
  
  
  RESULTS
  Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β1-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β1 significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation.
  
  
  CONCLUSIONS
  Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan.
authors.forename: Ching-Min
authors.initials: CM
authors.lastname: Tseng
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Hsiao
authors.forename: Vincent Yi-Fong
authors.initials: VY
authors.lastname: Su
authors.forename: Kang-Cheng
authors.initials: KC
authors.lastname: Su
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Wu
authors.forename: Kuo-Ting
authors.initials: KT
authors.lastname: Chang
authors.forename: Diahn-Warng
authors.initials: DW
authors.lastname: Perng
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006097:Granulation Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; C497790:SMAD3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D003094:Collagen; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3