Hill, Charlotte, Li, Juanjuan, Liu, Dian, Conforti, Franco, Brereton, Christopher J, Yao, Liudi, Zhou, Yilu, Alzetani, Aiman, Chee, Serena J, Marshall, Ben G et al (show 10 more authors)
(2019)
Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis.
CELL DEATH & DISEASE, 10 (8).
591-.
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Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fi.pdf - Other Download (6MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Lung, Fibroblasts, Humans, Lung Neoplasms, Transcription Factors, Risk Factors, Cell Differentiation, Aging, Autophagy, Transcription Factor RelA, Idiopathic Pulmonary Fibrosis, Myofibroblasts, Epithelial-Mesenchymal Transition, Primary Cell Culture, Alveolar Epithelial Cells, Snail Family Transcription Factors, Sequestosome-1 Protein, A549 Cells |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 Apr 2023 09:22 |
| Last Modified: | 19 Apr 2023 09:22 |
| DOI: | 10.1038/s41419-019-1820-x |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169673 |
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