Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease.

Academic Article


  • RATIONALE: TGF-β, a mediator of pulmonary fibrosis, is a genetic modifier of CF respiratory deterioration. The mechanistic relationship between TGF-β signaling and CF lung disease has not been determined. OBJECTIVE: To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling may contribute to pulmonary decline, airway remodeling and tissue fibrosis. METHODS: Lung samples from CF and non-CF subjects were analyzed morphometrically for total TGF-β1, TGF-β signaling (Smad2 phosphorylation), myofibroblast differentiation (α-smooth muscle actin), and collagen deposition (Masson trichrome stain). RESULTS: TGF-β signaling and fibrosis are markedly increased in CF (p<0.01), and the presence of myofibroblasts is four-fold higher in CF vs. normal lung tissue (p<0.005). In lung tissue with prominent TGF-β signaling, both myofibroblast differentiation and tissue fibrosis are significantly augmented (p<0.005). CONCLUSIONS: These studies establish for the first time that a pathogenic mechanism described previously in pulmonary fibrosis is also prominent in cystic fibrosis lung disease. The presence of TGF-β dependent signaling in areas of prominent myofibroblast proliferation and fibrosis in CF suggests that strategies under development for other pro-fibrotic lung conditions may also be evaluated for use in CF.
  • Published In

  • PLoS ONE  Journal
  • Keywords

  • Adult, Cell Differentiation, Cystic Fibrosis, Female, Fibrosis, Humans, Idiopathic Pulmonary Fibrosis, Lung, Male, Middle Aged, Models, Biological, Myofibroblasts, Phosphorylation, Signal Transduction, Smad2 Protein, Transforming Growth Factor beta, Transforming Growth Factor beta1
  • Digital Object Identifier (doi)

    Author List

  • Harris WT; Kelly DR; Zhou Y; Wang D; MacEwen M; Hagood JS; Clancy JP; Ambalavanan N; Sorscher EJ
  • Start Page

  • e70196
  • Volume

  • 8
  • Issue

  • 8