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Nogo-B promotes epithelial-mesenchymal transition in lung fibrosis via PERK branch of the endoplasmic reticulum stress pathway
- Source :
- Ann Transl Med
- Publication Year :
- 2021
- Publisher :
- AME Publishing Company, 2021.
-
Abstract
- Background Idiopathic pulmonary fibrosis (IPF) is a fatal chronic pulmonary fibrosis disease and pathological mechanisms of fibrogenesis in IPF are still to be elucidated. Here, we investigated the potential role of Nogo-B in pulmonary fibrogenesis. Methods A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). Lung epithelial cells MLE-12 and TC-1 JHU-1 were cultured for TGF-β treatment. The extent of lung fibrosis was evaluated using hematoxylin and eosin (HE) staining and Masson staining in model mice and Nogo-B knockout mice. The protein levels of Nogo-B, endoplasmic reticulum stress (ERS) sensors including PERK, IRE1α, ATF6 and epithelial-mesenchymal transition (EMT) markers including E-cadherin and N-cadherin, vimentin were assayed by Western blotting respectively after Nogo-B knockdown or overexpression with lentivirus. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate cytokine levels of TGF-β, TNF-α, IL-1β, IL-6 and IL-10 in bronchoalveolar lavage fluid (BALF). Results Nogo-B expression was up-regulated in lung tissues of fibrosis model mice and alveolar epithelial cells. Nogo-B knockdown significantly attenuated lung fibrogenesis, downregulated the levels of inflammatory cytokines, inhibited EMT as well as decreased the level of phosphor-PERK/PERK but not the levels of phosphor-IRE1α/IRE1α and c-ATF6. Additionally, a potential efficacy of PERK blockade was demonstrated in improving the extent of lung fibrosis in model mice. Conclusions This study discovered that involvement of Nogo-B in pulmonary fibrogenesis was associated with the PERK branch of ERS pathway and EMT. Nogo-B could be considered as a potential therapeutic target for the treatment of IPF.
- Subjects :
- 0301 basic medicine
Lung
medicine.diagnostic_test
business.industry
General Medicine
respiratory system
Bleomycin
medicine.disease
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
Idiopathic pulmonary fibrosis
030104 developmental biology
0302 clinical medicine
Bronchoalveolar lavage
medicine.anatomical_structure
chemistry
Fibrosis
030220 oncology & carcinogenesis
Pulmonary fibrosis
medicine
Cancer research
Original Article
Epithelial–mesenchymal transition
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Ann Transl Med
- Accession number :
- edsair.doi.dedup.....abef02ca331d31984a08c700309aae05