Yao, Liudi, Conforti, Franco, Hill, Charlotte, Bell, Joseph, Drawater, Leena, Li, Juanjuan, Liu, Dian, Xiong, Hua, Alzetani, Aiman, Chee, Serena J., Marshall, Ben G., Fletcher, Sophie, Hancock, David, Coldwell, Mark, Yuan, Xianglin, Ottensmeier, Christian, Downward, Julian, Collins, Jane, Ewing, Robert, Richeldi, Luca, Skipp, Paul, Jones, Mark, Davies, Donna and Wang, Yihua (2019) Paracrine signalling during ZEB1-mediated epithelial mesenchymal transition augments local myofibroblast differentiation in lung fibrosis. Cell Death and Differentiation, 26 (5), 943-957. (doi:10.1038/s41418-018-0175-7).
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 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 information
Identifiers
Catalogue record
Export record
Altmetrics
Contributors
University divisions
- Current Faculties > Faculty of Environmental and Life Sciences > School of Biological Sciences > Plants and Food Security
School of Biological Sciences > Plants and Food Security - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Institute for Life Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg)
Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg) - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Biological Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > School of Biological Sciences > Biological Sciences (pre 2018 reorg)
School of Biological Sciences > Biological Sciences (pre 2018 reorg) - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Biological Sciences (pre 2018 reorg) > Molecular and Cellular (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > School of Biological Sciences > Biological Sciences (pre 2018 reorg) > Molecular and Cellular (pre 2018 reorg)
School of Biological Sciences > Biological Sciences (pre 2018 reorg) > Molecular and Cellular (pre 2018 reorg) - Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Clinical & Experimental Sciences (pre 2018 reorg)
Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg)
Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg) - Faculties (pre 2018 reorg) > Faculty of Engineering and the Environment (pre 2018 reorg) > Southampton Marine & Maritime Institute (pre 2018 reorg)
- Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Biological Sciences (pre 2018 reorg) > Biomedicine (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > School of Biological Sciences > Biological Sciences (pre 2018 reorg) > Biomedicine (pre 2018 reorg)
School of Biological Sciences > Biological Sciences (pre 2018 reorg) > Biomedicine (pre 2018 reorg) - Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Cancer Sciences (pre 2018 reorg)
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.