Source:http://linkedlifedata.com/resource/pubmed/id/20693406
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2011-6-9
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pubmed:abstractText |
The histopathology of idiopathic pulmonary fibrosis (IPF) includes the presence of myofibroblasts within so-called fibroblastic foci, and studies suggest that lung myofibroblasts may be derived from epithelial cells through epithelial--mesenchymal transition (EMT). Transforming growth factor (TGF)-?1 is expressed and/or activated in fibrogenesis, and induces EMT in lung epithelial cells in a dose-dependent manner. A higher occurrence of Epstein-Barr virus (EBV) has been reported in the lung tissue of patients with IPF. EBV expresses latent membrane protein (LMP) 1 during the latent phase of infection, and may play a role in the pathogenesis of pulmonary fibrosis inasmuch as LMP-1 may act as a constitutively active TNF-? receptor. Our data show a remarkable increase in mesenchymal cell markers, along with a concurrent reduction in the expression of epithelial cell markers in lung epithelial cells cotreated with LMP-1, and very low doses of TGF-?1. This effect was mirrored in lung epithelial cells infected with EBV expressing LMP1 and cotreated with TGF-?1. LMP1 pro-EMT signaling was identified, and occurs primarily through the nuclear factor-?B pathway and secondarily through the extracellular signal--regulated kinase (ERK) pathway. Activation of the ERK pathway was shown to be critical for aspects of TGF-?1-induced EMT. LMP1 accentuates the TGF-?1 activation of ERK. Together, these data demonstrate that the presence of EBV-LMP1 in lung epithelial cells synergizes with TGF-?1 to induce EMT. Our in vitro data may help to explain the observation that patients with IPF demonstrating positive staining for LMP1 in lung epithelial cells have a more rapid demise than patients in whom LMP1 is not detected.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/EBV-associated membrane antigen...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Matrix Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1535-4989
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
852-62
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pubmed:meshHeading |
pubmed-meshheading:20693406-Cell Line, Tumor,
pubmed-meshheading:20693406-Cell Movement,
pubmed-meshheading:20693406-Epithelial Cells,
pubmed-meshheading:20693406-Epithelial-Mesenchymal Transition,
pubmed-meshheading:20693406-Fibrosis,
pubmed-meshheading:20693406-Herpesvirus 4, Human,
pubmed-meshheading:20693406-Humans,
pubmed-meshheading:20693406-Lung,
pubmed-meshheading:20693406-Mesoderm,
pubmed-meshheading:20693406-Models, Biological,
pubmed-meshheading:20693406-NF-kappa B,
pubmed-meshheading:20693406-Signal Transduction,
pubmed-meshheading:20693406-Transforming Growth Factor beta1,
pubmed-meshheading:20693406-Viral Matrix Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
The Epstein-Barr virus latent membrane protein 1 and transforming growth factor--?1 synergistically induce epithelial--mesenchymal transition in lung epithelial cells.
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pubmed:affiliation |
Department of Medicine, Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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