dc.contributor.author | Yao, L | |
dc.contributor.author | Zhou, Y | |
dc.contributor.author | Li, J | |
dc.contributor.author | Wickens, L | |
dc.contributor.author | Conforti, F | |
dc.contributor.author | Rattu, A | |
dc.contributor.author | Ibrahim, FM | |
dc.contributor.author | Alzetani, A | |
dc.contributor.author | Marshall, BG | |
dc.contributor.author | Fletcher, SV | |
dc.contributor.author | Hancock, D | |
dc.contributor.author | Wallis, T | |
dc.contributor.author | Downward, J | |
dc.contributor.author | Ewing, RM | |
dc.contributor.author | Richeldi, L | |
dc.contributor.author | Skipp, P | |
dc.contributor.author | Davies, DE | |
dc.contributor.author | Jones, MG | |
dc.contributor.author | Wang, Y | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-09-13T10:03:19Z | |
dc.date.available | 2022-09-13T10:03:19Z | |
dc.date.issued | 2021-09-01 | |
dc.identifier | ARTN 101096 | |
dc.identifier | S0021-9258(21)00899-1 | |
dc.identifier.citation | Journal of Biological Chemistry, 2021, 297 (3), pp. 101096 - | en_US |
dc.identifier.issn | 0021-9258 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5454 | |
dc.identifier.eissn | 1083-351X | |
dc.identifier.eissn | 1083-351X | |
dc.identifier.doi | 10.1016/j.jbc.2021.101096 | |
dc.description.abstract | Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2 to 4 years. Injury to and/or dysfunction of the alveolar epithelium is strongly implicated in IPF disease initiation, but the factors that determine whether fibrosis progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated that zinc finger E-box-binding homeobox 1-mediated epithelial-mesenchymal transition in human alveolar epithelial type II (ATII) cells augments transforming growth factor-β-induced profibrogenic responses in underlying lung fibroblasts via paracrine signaling. Here, we investigated bidirectional epithelial-mesenchymal crosstalk and its potential to drive fibrosis progression. RNA-Seq of lung fibroblasts exposed to conditioned media from ATII cells undergoing RAS-induced epithelial-mesenchymal transition identified many differentially expressed genes including those involved in cell migration and extracellular matrix regulation. We confirmed that paracrine signaling between RAS-activated ATII cells and fibroblasts augmented fibroblast recruitment and demonstrated that this involved a zinc finger E-box-binding homeobox 1-tissue plasminogen activator axis. In a reciprocal fashion, paracrine signaling from transforming growth factor-β-activated lung fibroblasts or IPF fibroblasts induced RAS activation in ATII cells, at least partially through the secreted protein acidic and rich in cysteine, which may signal via the epithelial growth factor receptor via epithelial growth factor-like repeats. Together, these data identify that aberrant bidirectional epithelial-mesenchymal crosstalk in IPF drives a chronic feedback loop that maintains a wound-healing phenotype and provides self-sustaining profibrotic signals. | |
dc.format | Print-Electronic | |
dc.format.extent | 101096 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | ELSEVIER | en_US |
dc.relation.ispartof | Journal of Biological Chemistry | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | EGFR | |
dc.subject | RAS | |
dc.subject | SPARC | |
dc.subject | TGF-β | |
dc.subject | ZEB1 | |
dc.subject | epithelial–mesenchymal transition | |
dc.subject | pulmonary fibrosis | |
dc.subject | Cell Movement | |
dc.subject | Epithelial Cells | |
dc.subject | Epithelial-Mesenchymal Transition | |
dc.subject | Extracellular Matrix | |
dc.subject | Female | |
dc.subject | Fibroblasts | |
dc.subject | Fibrosis | |
dc.subject | Humans | |
dc.subject | Idiopathic Pulmonary Fibrosis | |
dc.subject | Lung | |
dc.subject | Male | |
dc.subject | Primary Cell Culture | |
dc.subject | Pulmonary Fibrosis | |
dc.subject | Tissue Plasminogen Activator | |
dc.subject | Transforming Growth Factor beta | |
dc.subject | Zinc Finger E-box-Binding Homeobox 1 | |
dc.title | Bidirectional epithelial-mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-08-17 | |
dc.date.updated | 2022-09-13T10:01:15Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1016/j.jbc.2021.101096 | en_US |
rioxxterms.licenseref.startdate | 2021-09-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/34418430 | |
pubs.issue | 3 | |
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.publisher-url | http://dx.doi.org/10.1016/j.jbc.2021.101096 | |
pubs.volume | 297 | |
icr.researchteam | Lung Cancer Group | en_US |
dc.contributor.icrauthor | Downward, Julian David Harry | |
icr.provenance | Deposited by Mr Arek Surman on 2022-09-13. Deposit type is initial. No. of files: 1. Files: Bidirectional epithelial-mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis.pdf | |