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Twist: a regulator of epithelial-mesenchymal transition in lung fibrosis
- Source :
- PLoS ONE, PLoS ONE, Vol 4, Iss 10, p e7559 (2009)
- Publication Year :
- 2009
-
Abstract
- Background Several studies have implicated viral infection as an important factor in the pathogenesis of IPF and related fibrotic lung disorders. Viruses are thought to cause epithelial cell injury and promote epithelial-mesenchymal transition (EMT), a process whereby differentiated epithelial cells undergo transition to a mesenchymal phenotype, and considered a source of fibroblasts in the setting of lung injury. We have demonstrated an association between the epithelial injury caused by chronic herpes virus infection with the murine gamma-herpes virus, MHV68, and lung fibrosis. We hypothesize that EMT in this model of virus-induced pulmonary fibrosis is driven by the expression of the transcription factor Twist. Methods/findings In vitro MHV68 infection of murine lung epithelial cells induced expression of Twist, and mesenchymal markers. Stable overexpression of Twist promoted EMT in MLE15 lung epithelial cells. Transient knockdown expression of Twist resulted in preservation of epithelial phenotype after in vitro MHV68 infection. In concordance, high expression of Twist was found in lung epithelial cells of MHV68 infected mice, but not in mock infected mice. Alveolar epithelial cells from lung tissue of idiopathic pulmonary fibrosis (IPF) patients were strongly positive for Twist. These cells demonstrated features of EMT with low expression of E-cadherin and upregulation of the mesenchymal marker N-cadherin. Finally, IPF tissue with high Twist protein levels was also positive for the herpesvirus, EBV. Conclusions/significance We conclude that Twist contributes to EMT in the model of virus-induced pulmonary fibrosis. We speculate that in some IPF cases, gamma-herpes virus infection with EBV might be a source of injury precipitating EMT through the expression of Twist.
- Subjects :
- Pathology
medicine.medical_specialty
Pulmonary Fibrosis
lcsh:Medicine
Lung injury
Biology
Respiratory Medicine/Respiratory Infections
Epithelium
Lung Disorder
Mesoderm
03 medical and health sciences
Twist transcription factor
Idiopathic pulmonary fibrosis
Mice
0302 clinical medicine
Respiratory Medicine/Interstitial Lung Diseases
Fibrosis
Pulmonary fibrosis
medicine
Animals
Humans
Epithelial–mesenchymal transition
lcsh:Science
Lung
Herpesviridae
030304 developmental biology
0303 health sciences
Multidisciplinary
lcsh:R
Twist-Related Protein 1
Nuclear Proteins
Epithelial Cells
Herpesviridae Infections
Cell Biology
respiratory system
medicine.disease
Cadherins
3. Good health
respiratory tract diseases
Pulmonary Alveoli
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
lcsh:Q
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....52957a891961801c78dfd2338a9fb5a0