Paracrine signalling during ZEB1-mediated epithelial–mesenchymal transition augments local myofibroblast differentiation in lung fibrosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-05

AUTHORS

Liudi Yao, Franco Conforti, Charlotte Hill, Joseph Bell, Leena Drawater, Juanjuan Li, Dian Liu, Hua Xiong, Aiman Alzetani, Serena J. Chee, Ben G. Marshall, Sophie V. Fletcher, David Hancock, Mark Coldwell, Xianglin Yuan, Christian H. Ottensmeier, Julian Downward, Jane E. Collins, Rob M. Ewing, Luca Richeldi, Paul Skipp, Mark G. Jones, Donna E. Davies, Yihua Wang

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. More... »

PAGES

1-15

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41418-018-0175-7

    DOI

    http://dx.doi.org/10.1038/s41418-018-0175-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105852859

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30050057


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    423 https://www.grid.ac/institutes/grid.5491.9 schema:alternateName University of Southampton
    424 schema:name Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, SO17 1BJ, Southampton, UK
    425 Cancer Sciences & NIHR and CRUK Experimental Cancer Sciences Unit, University of Southampton, SO16 6YD, Southampton, UK
    426 Centre for Proteomic Research, Institute for Life Sciences University of Southampton, SO17 1BJ, Southampton, UK
    427 Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, SO16 6YD, Southampton, UK
    428 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China
    429 Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK
    430 NIHR Southampton Biomedical Research Centre, University Hospital Southampton, SO16 6YD, Southampton, UK
    431 University Hospital Southampton, SO16 6YD, Southampton, UK
    432 rdf:type schema:Organization
    433 https://www.grid.ac/institutes/grid.8142.f schema:alternateName Catholic University of the Sacred Heart
    434 schema:name Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, SO16 6YD, Southampton, UK
    435 NIHR Southampton Biomedical Research Centre, University Hospital Southampton, SO16 6YD, Southampton, UK
    436 Unità Operativa Complessa di Pneumologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli, Rome, Italy
    437 rdf:type schema:Organization
     




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