dc.contributor.author | Yao, L | |
dc.contributor.author | Conforti, F | |
dc.contributor.author | Hill, C | |
dc.contributor.author | Bell, J | |
dc.contributor.author | Drawater, L | |
dc.contributor.author | Li, J | |
dc.contributor.author | Liu, D | |
dc.contributor.author | Xiong, H | |
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 | Coldwell, M | |
dc.contributor.author | Yuan, X | |
dc.contributor.author | Ottensmeier, CH | |
dc.contributor.author | Downward, J | |
dc.contributor.author | Collins, JE | |
dc.contributor.author | Ewing, RM | |
dc.contributor.author | Richeldi, L | |
dc.contributor.author | Skipp, P | |
dc.contributor.author | Jones, MG | |
dc.contributor.author | Davies, DE | |
dc.contributor.author | Wang, Y | |
dc.date.accessioned | 2020-06-08T15:04:19Z | |
dc.date.issued | 2019-05 | |
dc.identifier.citation | Cell death and differentiation, 2019, 26 (5), pp. 943 - 957 | |
dc.identifier.issn | 1350-9047 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3706 | |
dc.identifier.eissn | 1476-5403 | |
dc.identifier.doi | 10.1038/s41418-018-0175-7 | |
dc.description.abstract | The contribution of epithelial-mesenchymal transition (EMT) to human lung fibrogenesis is controversial. Here we provide evidence that ZEB1-mediated EMT in human alveolar epithelial type II (ATII) cells contributes to the development of lung fibrosis by paracrine signalling to underlying fibroblasts. Activation of EGFR-RAS-ERK signalling in ATII cells induced EMT via ZEB1. ATII cells had extremely low extracellular matrix gene expression even after induction of EMT, however conditioned media from ATII cells undergoing RAS-induced EMT augmented TGFβ-induced profibrogenic responses in lung fibroblasts. This epithelial-mesenchymal crosstalk was controlled by ZEB1 via the expression of tissue plasminogen activator (tPA). In human fibrotic lung tissue, nuclear ZEB1 expression was detected in alveolar epithelium adjacent to sites of extracellular matrix (ECM) deposition, suggesting that ZEB1-mediated paracrine signalling has the potential to contribute to early fibrotic changes in the lung interstitium. Targeting this novel ZEB1 regulatory axis may be a viable strategy for the treatment of pulmonary fibrosis. | |
dc.format | Print-Electronic | |
dc.format.extent | 943 - 957 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Lung | |
dc.subject | Cell Line | |
dc.subject | Extracellular Matrix | |
dc.subject | Epithelial Cells | |
dc.subject | Humans | |
dc.subject | Respiratory Tract Diseases | |
dc.subject | Fibrosis | |
dc.subject | Paracrine Communication | |
dc.subject | Cell Differentiation | |
dc.subject | Gene Expression Regulation | |
dc.subject | Myofibroblasts | |
dc.subject | Epithelial-Mesenchymal Transition | |
dc.subject | Zinc Finger E-box-Binding Homeobox 1 | |
dc.title | Paracrine signalling during ZEB1-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in lung fibrosis. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-07-09 | |
rioxxterms.versionofrecord | 10.1038/s41418-018-0175-7 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell death and differentiation | |
pubs.issue | 5 | |
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.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 | 26 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Lung Cancer Group | en_US |
dc.contributor.icrauthor | Downward, Julian David Harry | |