{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sides MD"],"funding":["NHLBI NIH HHS","NCI NIH HHS"],"pagination":["852-62"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3135845"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(6)"],"pubmed_abstract":["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)-β1 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-α 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-β1. This effect was mirrored in lung epithelial cells infected with EBV expressing LMP1 and cotreated with TGF-β1. LMP1 pro-EMT signaling was identified, and occurs primarily through the nuclear factor-κB 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-β1-induced EMT. LMP1 accentuates the TGF-β1 activation of ERK. Together, these data demonstrate that the presence of EBV-LMP1 in lung epithelial cells synergizes with TGF-β1 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."],"journal":["American journal of respiratory cell and molecular biology"],"pubmed_title":["The Epstein-Barr virus latent membrane protein 1 and transforming growth factor--β1 synergistically induce epithelial--mesenchymal transition in lung epithelial cells."],"pmcid":["PMC3135845"],"funding_grant_id":["R01HL083901","R01 CA138268"],"pubmed_authors":["Takahashi T","Sides MD","Klingsberg RC","Lasky JA","Gordon KA","Lin Z","Shan B","Flemington EK","Nguyen HT"],"additional_accession":[]},"is_claimable":false,"name":"The Epstein-Barr virus latent membrane protein 1 and transforming growth factor--β1 synergistically induce epithelial--mesenchymal transition in lung epithelial cells.","description":"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)-β1 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-α 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-β1. This effect was mirrored in lung epithelial cells infected with EBV expressing LMP1 and cotreated with TGF-β1. LMP1 pro-EMT signaling was identified, and occurs primarily through the nuclear factor-κB 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-β1-induced EMT. LMP1 accentuates the TGF-β1 activation of ERK. Together, these data demonstrate that the presence of EBV-LMP1 in lung epithelial cells synergizes with TGF-β1 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.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Jun","modification":"2025-04-04T23:39:49.792Z","creation":"2019-03-27T03:07:03Z"},"accession":"S-EPMC3135845","cross_references":{"pubmed":["20693406"],"doi":["10.1165/rcmb.2009-0232OC","10.1165/rcmb.2009-0232oc"]}}