Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial-mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the p...

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Bibliographic Details
Published in:Bioscience reports 2020-01, Vol.40 (1)
Main Authors: Weng, Chang-Mei, Li, Qing, Chen, Kui-Jun, Xu, Cheng-Xiong, Deng, Meng-Sheng, Li, Tao, Zhang, Dong-Dong, Duan, Zhao-Xia, Chen, Zhi-Qiang, Li, Guan-Hua, Chen, Jing, Wang, Jian-Min
Format: Article
Language:English
Subjects:
A549 Cells
Animals
Bleomycin
Chemical Biology
Disease Models, Animal
Epithelial-Mesenchymal Transition - drug effects
Fibroblast Growth Factor 2 - metabolism
Fibroblast Growth Factor 2 - pharmacology
Gene Expression & Regulation
Humans
Idiopathic Pulmonary Fibrosis - chemically induced
Idiopathic Pulmonary Fibrosis - enzymology
Idiopathic Pulmonary Fibrosis - genetics
Idiopathic Pulmonary Fibrosis - pathology
Lung - drug effects
Lung - enzymology
Lung - pathology
Male
Mice
Molecular Interactions
Phosphatidylinositol 3-Kinase - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Signal Transduction
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta1 - pharmacology
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Summary:Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial-mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the pulmonary fibrosis inducer bleomycin simultaneously increased the expression of bFGF and TGF-β1 and inhibited epithelial-specific regulatory protein (ESRP1) expression in vivo and in vitro. In addition, in vitro experiments showed that bFGF and TGF-β1 down-regulated the expression of ESRP1 and that silencing ESRP1 promoted EMT in A549 cells. Notably, we determined that bFGF activates PI3K/Akt signaling, and treatment with the PI3K/Akt inhibitor LY294002 inhibited bleomycin-induced cell morphology changes and EMT. In addition, the effects of LY294002 on bleomycin-induced EMT were inhibited by ESRP1 silencing in A549 cells. Taken together, these findings suggest that bleomycin induced EMT through down-regulating ESRP1 by simultaneously increasing bFGF and TGF-β1 in pulmonary fibrosis. Additionally, our findings indicated that bFGF inhibits ESRP1 by activating PI3K/Akt signaling.
ISSN:0144-8463
1573-4935
DOI:10.1042/bsr20190756