Inhibition of mTOR ameliorates bleomycin-induced pulmonary fibrosis by regulating epithelial-mesenchymal transition.
Biochem Biophys Res Commun
; 500(4): 839-845, 2018 06 12.
Article
em En
| MEDLINE
| ID: mdl-29704504
Epithelial-mesenchymal transition (EMT) plays a pivotal role in idiopathic pulmonary fibrosis (IPF). In bleomycin-induced pulmonary fibrosis mice, we observed that inhibition of mTOR (mammalia target of rapamycin) attenuated IPF. Rapamycin suppressed the down-regulation of E-cadherin and up-regulation of fibronectin in bleomycin-induced pulmonary fibrosis mice. In addition, dual immunofluorescence staining for E-cadherin and fibronectin demonstrated that rapamycin pretreatment decreased the proportions of AECs undergoing EMT in bleomycin-induced pulmonary fibrosis, indicating that mTOR inhibition suppressed EMT in vivo. In the setting of transforming growth factor (TGF)-ß1-induced EMT in AECs, we found that mTOR inhibitor attenuated TGF-ß1-induced EMT in AECs. This EMT was characterized by morphology and cell skeleton changes and the expression of EMT phenotype markers. Finally, mTOR blockade decreased S6k and TGF-ß1-induced Smad2/3 phosphorylation. Bleomycin induced pulmonary fibrosis and EMT in mice, while mTOR repression inhibited bleomycin-induced pulmonary fibrosis and attenuated EMT in vivo. Hence, our study provided evidence of a novel mechanism by which mTOR inhibitor ameliorates pulmonary fibrosis. Suppression of mTOR and EMT may be a target for treatment of pulmonary fibrosis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alvéolos Pulmonares
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Fibrose Pulmonar
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Sirolimo
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Serina-Treonina Quinases TOR
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Transição Epitelial-Mesenquimal
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article