Abstract:
:The mTOR pathway is one of the key signal cascades in the pathogenesis of idiopathic pulmonary fibrosis. Previous studies have mainly focused on this pathway in the fibroblasts and/or myofibroblasts, but not in the epithelial cells. In this study, we sought to investigate the role of the mTOR pathway in lung epithelial cells in lung fibrosis. Using Sftpc-mTOR SL1+IT transgenic mice, in which active mTOR is conditionally expressed in lung epithelial cells, we assessed the effects of chronically activated mTOR in lung epithelial cells on lung phenotypes as well as bleomycin-induced lung fibrosis. Furthermore, we isolated alveolar epithelial cell type 2 from mice and performed RNA sequencing. Sftpc-mTOR SL1+IT transgenic mice had no obvious abnormal findings, but, after bleomycin administration, showed more severe fibrotic changes and lower lung compliance than control mice. RNA sequencing revealed Angptl4 (angiopoietin-like protein 4) as a candidate downstream gene of the mTOR pathway. In vitro studies revealed that ANGPTL4, as well as mTOR, promoted tight junction vulnerability and epithelial-mesenchymal transition. mTOR activation in lung epithelial cells promoted lung fibrosis and the expression of ANGPTL4, a novel downstream target of the mTOR pathway, which could be related to the etiology of fibrosis.
journal_name
Am J Respir Cell Mol Biolauthors
Saito M,Mitani A,Ishimori T,Miyashita N,Isago H,Mikami Y,Noguchi S,Tarui M,Nagase Tdoi
10.1165/rcmb.2019-0255OCsubject
Has Abstractpub_date
2020-06-01 00:00:00pages
699-708issue
6eissn
1044-1549issn
1535-4989journal_volume
62pub_type
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