Inhibition of mTOR ameliorates bleomycin-induced pulmonary fibrosis by regulating epithelial-mesenchymal transition

Journal Article · Fri Jun 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.04.148· OSTI ID:23137076

Han, Qian; Lin, Lianjun ^[1]; Zhao, Beilei ^[2]; Wang, Nanping ^[2]; Liu, Xinmin ^[1]

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1. The Geriatrics Department, Peking University First Hospital, Beijing (China)
2. Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Peking University Health Science Center, Beijing (China)

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)-β1-induced EMT in AECs, we found that mTOR inhibitor attenuated TGF-β1-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-β1-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.

• OSTI ID: 23137076
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 500; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLEOMYCIN
FIBROSIS
GROWTH FACTORS
MICE
PHOSPHORYLATION