Journal article
Autophagy inhibition-mediated epithelial–mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis
- Abstract:
- Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a risk factor for IPF and incidence has been demonstrated to increase with age. Decreased (macro)autophagy with age has been reported extensively in a variety of systems and diseases, including IPF. However, it is undetermined whether the role of faulty autophagy is causal or coincidental in the context of IPF. Here, we report that in alveolar epithelial cells inhibition of autophagy promotes epithelial–mesenchymal transition (EMT), a process implicated in embryonic development, wound healing, cancer metastasis and fibrosis. We further demonstrate that this is attained, at least in part, by increased p62/SQSTM1 expression that promotes p65/RELA mediated-transactivation of an EMT transcription factor, Snail2 (SNAI2), which not only controls EMT but also regulates the production of locally acting profibrogenic mediators. Our data suggest that reduced autophagy induces EMT of alveolar epithelial cells and can contribute to fibrosis via aberrant epithelial–fibroblast crosstalk.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 6.4MB, Terms of use)
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- Publisher copy:
- 10.1038/s41419-019-1820-x
Authors
+ Academy of Medical Sciences/Wellcome Trust
More from this funder
- Grant:
- Springboard Award: SBF002/1038
- Publisher:
- Springer Nature
- Journal:
- Cell Death and Disease More from this journal
- Volume:
- 10
- Article number:
- 591
- Publication date:
- 2019-08-07
- Acceptance date:
- 2019-07-18
- DOI:
- EISSN:
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2041-4889
- Pubs id:
-
pubs:1033501
- UUID:
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uuid:b7785c50-166c-4035-90d4-02390a6adaea
- Local pid:
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pubs:1033501
- Source identifiers:
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1033501
- Deposit date:
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2019-07-19
Terms of use
- Copyright holder:
- Hill et al
- Copyright date:
- 2019
- Notes:
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© The Author(s) 2019
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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