Open AccessAstragaloside IV modulates TGF ‐β1‐dependent epithelial‐mesenchymal transition in bleomycin‐induced pulmonary fibrosis
Author(s) -
Qian Weibin,
Cai Xinrui,
Qian Qiuhai,
Zhang Wei,
Wang Dongli
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13725
Subject(s) - epithelial–mesenchymal transition , pulmonary fibrosis , protein kinase b , bleomycin , cancer research , transforming growth factor , chemistry , idiopathic pulmonary fibrosis , a549 cell , fibrosis , cardiac fibrosis , pi3k/akt/mtor pathway , signal transduction , microbiology and biotechnology , medicine , biology , downregulation and upregulation , lung , cell , biochemistry , chemotherapy , gene
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‐β1 ( TGF ‐β1) was found to be up‐regulated, whereas Forkhead box O3a ( FOXO 3a) was hyperphosphorylated and less expressed. However, ASV treatment inhibited increased TGF ‐β1 and activated FOXO 3a in lung tissues. TGF ‐β1 was administered to alveolar epithelial cells A549 to induce EMT in vitro. Meanwhile, stimulation with TGF ‐β1‐activated phosphatidylinositol 3 kinase/protein kinase B ( PI 3K/Akt) pathway and induced FOXO 3a hyperphosphorylated and down‐regulated. It was found that overexpression of FOXO 3a leading to the suppression of TGF ‐β1‐induced EMT . Moreover, ASV treatment, similar with the TGF ‐β1 or PI 3K/Akt inhibitor, reverted these cellular changes and inhibited EMT in A549 cells. Collectively, the results suggested that ASV significantly inhibited TGF ‐β1/ PI 3K/Akt‐induced FOXO 3a hyperphosphorylation and down‐regulation to reverse EMT during the progression of fibrosis.