Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo.
The Fra-1/AP-1 transcription factor plays a key role in tumor epithelial cell progression; however, its role in pathogenic lung fibrosis remains unclear. In the present study, using a genetic approach (Fra-1 deficient mice), we have demonstrated a novel regulatory (protective) role for Fra-1 in lung...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3404039?pdf=render |
| _version_ | 1818380969355247616 |
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| author | Subbiah Rajasekaran Michelle Vaz Sekhar P Reddy |
| author_facet | Subbiah Rajasekaran Michelle Vaz Sekhar P Reddy |
| author_sort | Subbiah Rajasekaran |
| collection | DOAJ |
| description | The Fra-1/AP-1 transcription factor plays a key role in tumor epithelial cell progression; however, its role in pathogenic lung fibrosis remains unclear. In the present study, using a genetic approach (Fra-1 deficient mice), we have demonstrated a novel regulatory (protective) role for Fra-1 in lung fibrosis. We found greater levels of progressive interstitial fibrosis, characterized by increased levels of inflammation, collagen accumulation, and profibrotic and fibrotic gene expression in the lungs of Fra-1(Δ/Δ) mice than in those of Fra-1(+/+) mice following bleomycin treatment. Fra-1 knockdown in human lung epithelial cells caused the upregulation of mesenchymal marker N-cadherin, concomitant with a downregulation of the epithelial phenotype marker E-cadherin, under basal conditions and in response to bleomycin and TGF-β1. Furthermore, Fra-1 knockdown caused an enhanced expression of type 1 collagen and the downregulation of collagenase (MMP-1 and MMP-13) gene expression in human lung epithelial cells. Collectively, our findings demonstrate that Fra-1 mediates anti-fibrotic effects in the lung through the modulation of proinflammatory, profibrotic and fibrotic gene expression, and suggests that the Fra-1 transcription factor may be a potential target for pulmonary fibrosis, a progressive disorder with poor prognosis and treatment. |
| first_indexed | 2024-12-14T02:27:07Z |
| format | Article |
| id | doaj.art-7ffa7296682748198adb575e66c93502 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T02:27:07Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7ffa7296682748198adb575e66c935022022-12-21T23:20:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4161110.1371/journal.pone.0041611Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo.Subbiah RajasekaranMichelle VazSekhar P ReddyThe Fra-1/AP-1 transcription factor plays a key role in tumor epithelial cell progression; however, its role in pathogenic lung fibrosis remains unclear. In the present study, using a genetic approach (Fra-1 deficient mice), we have demonstrated a novel regulatory (protective) role for Fra-1 in lung fibrosis. We found greater levels of progressive interstitial fibrosis, characterized by increased levels of inflammation, collagen accumulation, and profibrotic and fibrotic gene expression in the lungs of Fra-1(Δ/Δ) mice than in those of Fra-1(+/+) mice following bleomycin treatment. Fra-1 knockdown in human lung epithelial cells caused the upregulation of mesenchymal marker N-cadherin, concomitant with a downregulation of the epithelial phenotype marker E-cadherin, under basal conditions and in response to bleomycin and TGF-β1. Furthermore, Fra-1 knockdown caused an enhanced expression of type 1 collagen and the downregulation of collagenase (MMP-1 and MMP-13) gene expression in human lung epithelial cells. Collectively, our findings demonstrate that Fra-1 mediates anti-fibrotic effects in the lung through the modulation of proinflammatory, profibrotic and fibrotic gene expression, and suggests that the Fra-1 transcription factor may be a potential target for pulmonary fibrosis, a progressive disorder with poor prognosis and treatment.http://europepmc.org/articles/PMC3404039?pdf=render |
| spellingShingle | Subbiah Rajasekaran Michelle Vaz Sekhar P Reddy Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. PLoS ONE |
| title | Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. |
| title_full | Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. |
| title_fullStr | Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. |
| title_full_unstemmed | Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. |
| title_short | Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. |
| title_sort | fra 1 ap 1 transcription factor negatively regulates pulmonary fibrosis in vivo |
| url | http://europepmc.org/articles/PMC3404039?pdf=render |
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