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dc.contributor.authorHill, Cen_US
dc.contributor.authorLi, Jen_US
dc.contributor.authorLiu, Den_US
dc.contributor.authorConforti, Fen_US
dc.contributor.authorBrereton, CJen_US
dc.contributor.authorYao, Len_US
dc.contributor.authorZhou, Yen_US
dc.contributor.authorAlzetani, Aen_US
dc.contributor.authorChee, SJen_US
dc.contributor.authorMarshall, BGen_US
dc.contributor.authorFletcher, SVen_US
dc.contributor.authorHancock, Den_US
dc.contributor.authorOttensmeier, CHen_US
dc.contributor.authorSteele, AJen_US
dc.contributor.authorDownward, Jen_US
dc.contributor.authorRicheldi, Len_US
dc.contributor.authorLu, Xen_US
dc.contributor.authorDavies, DEen_US
dc.contributor.authorJones, MGen_US
dc.contributor.authorWang, Yen_US
dc.date.accessioned2020-06-03T10:39:03Z
dc.date.issued2019-08-07
dc.identifier.citationCell death & disease, 2019, 10 (8), pp. 591 - ?
dc.identifier.issn2041-4889
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3684
dc.identifier.eissn2041-4889
dc.identifier.doi10.1038/s41419-019-1820-x
dc.description.abstractIdiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a risk factor for IPF and incidence has been demonstrated to increase with age. Decreased (macro)autophagy with age has been reported extensively in a variety of systems and diseases, including IPF. However, it is undetermined whether the role of faulty autophagy is causal or coincidental in the context of IPF. Here, we report that in alveolar epithelial cells inhibition of autophagy promotes epithelial-mesenchymal transition (EMT), a process implicated in embryonic development, wound healing, cancer metastasis and fibrosis. We further demonstrate that this is attained, at least in part, by increased p62/SQSTM1 expression that promotes p65/RELA mediated-transactivation of an EMT transcription factor, Snail2 (SNAI2), which not only controls EMT but also regulates the production of locally acting profibrogenic mediators. Our data suggest that reduced autophagy induces EMT of alveolar epithelial cells and can contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.en_US
dc.formatElectronic
dc.format.extent591 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectLungen_US
dc.subjectFibroblastsen_US
dc.subjectHumansen_US
dc.subjectLung Neoplasmsen_US
dc.subjectTranscription Factorsen_US
dc.subjectRisk Factorsen_US
dc.subjectCell Differentiationen_US
dc.subjectAgingen_US
dc.subjectAutophagyen_US
dc.subjectTranscription Factor RelAen_US
dc.subjectIdiopathic Pulmonary Fibrosisen_US
dc.subjectMyofibroblastsen_US
dc.subjectEpithelial-Mesenchymal Transitionen_US
dc.subjectPrimary Cell Cultureen_US
dc.subjectAlveolar Epithelial Cellsen_US
dc.subjectSnail Family Transcription Factorsen_US
dc.subjectSequestosome-1 Proteinen_US
dc.subjectA549 Cellsen_US
dc.titleAutophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis.
dc.typeJournal Article
dcterms.dateAccepted2019-07-18
rioxxterms.versionofrecord10.1038/s41419-019-1820-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-08-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell death & diseaseen_US
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.publication-statusPublished
pubs.volume10en_US
pubs.embargo.termsNot known
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorDownward, Julian David Harryen


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