dc.contributor.author | Hill, C | |
dc.contributor.author | Li, J | |
dc.contributor.author | Liu, D | |
dc.contributor.author | Conforti, F | |
dc.contributor.author | Brereton, CJ | |
dc.contributor.author | Yao, L | |
dc.contributor.author | Zhou, Y | |
dc.contributor.author | Alzetani, A | |
dc.contributor.author | Chee, SJ | |
dc.contributor.author | Marshall, BG | |
dc.contributor.author | Fletcher, SV | |
dc.contributor.author | Hancock, D | |
dc.contributor.author | Ottensmeier, CH | |
dc.contributor.author | Steele, AJ | |
dc.contributor.author | Downward, J | |
dc.contributor.author | Richeldi, L | |
dc.contributor.author | Lu, X | |
dc.contributor.author | Davies, DE | |
dc.contributor.author | Jones, MG | |
dc.contributor.author | Wang, Y | |
dc.date.accessioned | 2020-06-03T10:39:03Z | |
dc.date.issued | 2019-08-07 | |
dc.identifier.citation | Cell death & disease, 2019, 10 (8), pp. 591 - ? | |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3684 | |
dc.identifier.eissn | 2041-4889 | |
dc.identifier.doi | 10.1038/s41419-019-1820-x | |
dc.description.abstract | Idiopathic 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. | |
dc.format | Electronic | |
dc.format.extent | 591 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Lung | |
dc.subject | Fibroblasts | |
dc.subject | Humans | |
dc.subject | Lung Neoplasms | |
dc.subject | Transcription Factors | |
dc.subject | Risk Factors | |
dc.subject | Cell Differentiation | |
dc.subject | Aging | |
dc.subject | Autophagy | |
dc.subject | Transcription Factor RelA | |
dc.subject | Idiopathic Pulmonary Fibrosis | |
dc.subject | Myofibroblasts | |
dc.subject | Epithelial-Mesenchymal Transition | |
dc.subject | Primary Cell Culture | |
dc.subject | Alveolar Epithelial Cells | |
dc.subject | Snail Family Transcription Factors | |
dc.subject | Sequestosome-1 Protein | |
dc.subject | A549 Cells | |
dc.title | Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-07-18 | |
rioxxterms.versionofrecord | 10.1038/s41419-019-1820-x | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-08-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell death & disease | |
pubs.issue | 8 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Lung Cancer Group | |
dc.contributor.icrauthor | Downward, Julian David Harry | |