Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease.
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.To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3741283?pdf=render |
| _version_ | 1818164291671425024 |
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| author | William T Harris David R Kelly Yong Zhou Dezhi Wang Mark MacEwen James S Hagood J P Clancy Namasivayam Ambalavanan Eric J Sorscher |
| author_facet | William T Harris David R Kelly Yong Zhou Dezhi Wang Mark MacEwen James S Hagood J P Clancy Namasivayam Ambalavanan Eric J Sorscher |
| author_sort | William T Harris |
| collection | DOAJ |
| description | 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.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.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).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).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. |
| first_indexed | 2024-12-11T17:03:07Z |
| format | Article |
| id | doaj.art-62491fbf949845a4a6e71a9d41869f93 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T17:03:07Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-62491fbf949845a4a6e71a9d41869f932022-12-22T00:57:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7019610.1371/journal.pone.0070196Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease.William T HarrisDavid R KellyYong ZhouDezhi WangMark MacEwenJames S HagoodJ P ClancyNamasivayam AmbalavananEric J SorscherTGF-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.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.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).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).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.http://europepmc.org/articles/PMC3741283?pdf=render |
| spellingShingle | William T Harris David R Kelly Yong Zhou Dezhi Wang Mark MacEwen James S Hagood J P Clancy Namasivayam Ambalavanan Eric J Sorscher Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. PLoS ONE |
| title | Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. |
| title_full | Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. |
| title_fullStr | Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. |
| title_full_unstemmed | Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. |
| title_short | Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. |
| title_sort | myofibroblast differentiation and enhanced tgf b signaling in cystic fibrosis lung disease |
| url | http://europepmc.org/articles/PMC3741283?pdf=render |
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