| First Author | Rajasekaran S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 7 | Pages | e41611 |
| PubMed ID | 22911824 | Mgi Jnum | J:189882 |
| Mgi Id | MGI:5447210 | Doi | 10.1371/journal.pone.0041611 |
| Citation | Rajasekaran S, et al. (2012) Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. PLoS One 7(7):e41611 |
| abstractText | 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(Delta/Delta) 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-beta1. 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. |
