Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 22, Issue 9, Pages 4354-4365Publisher
WILEY
DOI: 10.1111/jcmm.13725
Keywords
astragaloside IV; epithelial-mesenchymal transition; forkhead box O3a; idiopathic pulmonary fibrosis; transforming growth factor-beta 1
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Funding
- National Natural Science Foundation of China [81704071]
- Key Research and Development Plan of Shandong province [2018GSF119027]
- Taishan Scholar Program of Shandong Province in China of Pulmonary disease of traditional Chinese Medicine [ts201712096]
- Natural Science Foundation of Shandong Province [ZR2017BH027, ZR2016HB19]
- Innovation Project of Shandong Academy of Medical Sciences
- Technology Program of Shandong Academy of Medical Sciences [2015-31]
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Epithelial-mesenchymal transition (EMT) plays an important role in idiopathic pulmonary fibrosis (IPF). Astragaloside IV (ASV), a natural saponin from astragalus membranaceus, has shown anti-fibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. The current study was undertaken to determine whether EMT was involved in the beneficial of ASV against BLM-induced pulmonary fibrosis and to elucidate its potential mechanism. As expected, in BLM-induced IPF, ASV exerted protective effects on pulmonary fibrosis and ASV significantly reversed BLM-induced EMT. Intriguing, transforming growth factor-beta 1 (TGF-beta 1) was found to be up-regulated, whereas Forkhead box O3a (FOXO3a) was hyperphosphorylated and less expressed. However, ASV treatment inhibited increased TGF-beta 1 and activated FOXO3a in lung tissues. TGF-beta 1 was administered to alveolar epithelial cells A549 to induce EMT invitro. Meanwhile, stimulation with TGF-beta 1-activated phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway and induced FOXO3a hyperphosphorylated and down-regulated. It was found that overexpression of FOXO3a leading to the suppression of TGF-beta 1-induced EMT. Moreover, ASV treatment, similar with the TGF-beta 1 or PI3K/Akt inhibitor, reverted these cellular changes and inhibited EMT in A549 cells. Collectively, the results suggested that ASV significantly inhibited TGF-beta 1/PI3K/Akt-induced FOXO3a hyperphosphorylation and down-regulation to reverse EMT during the progression of fibrosis.
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