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dc.contributor.authorYao, L
dc.contributor.authorConforti, F
dc.contributor.authorHill, C
dc.contributor.authorBell, J
dc.contributor.authorDrawater, L
dc.contributor.authorLi, J
dc.contributor.authorLiu, D
dc.contributor.authorXiong, H
dc.contributor.authorAlzetani, A
dc.contributor.authorChee, SJ
dc.contributor.authorMarshall, BG
dc.contributor.authorFletcher, SV
dc.contributor.authorHancock, D
dc.contributor.authorColdwell, M
dc.contributor.authorYuan, X
dc.contributor.authorOttensmeier, CH
dc.contributor.authorDownward, J
dc.contributor.authorCollins, JE
dc.contributor.authorEwing, RM
dc.contributor.authorRicheldi, L
dc.contributor.authorSkipp, P
dc.contributor.authorJones, MG
dc.contributor.authorDavies, DE
dc.contributor.authorWang, Y
dc.date.accessioned2020-06-08T15:04:19Z
dc.date.issued2019-05
dc.identifier.citationCell death and differentiation, 2019, 26 (5), pp. 943 - 957
dc.identifier.issn1350-9047
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3706
dc.identifier.eissn1476-5403
dc.identifier.doi10.1038/s41418-018-0175-7
dc.description.abstractThe 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.formatPrint-Electronic
dc.format.extent943 - 957
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectLung
dc.subjectCell Line
dc.subjectExtracellular Matrix
dc.subjectEpithelial Cells
dc.subjectHumans
dc.subjectRespiratory Tract Diseases
dc.subjectFibrosis
dc.subjectParacrine Communication
dc.subjectCell Differentiation
dc.subjectGene Expression Regulation
dc.subjectMyofibroblasts
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectZinc Finger E-box-Binding Homeobox 1
dc.titleParacrine signalling during ZEB1-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in lung fibrosis.
dc.typeJournal Article
dcterms.dateAccepted2018-07-09
rioxxterms.versionofrecord10.1038/s41418-018-0175-7
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell death and differentiation
pubs.issue5
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.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.volume26
pubs.embargo.termsNot known
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorDownward, Julian David Harryen


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