RRC ID 58788
著者 Yamagami Y, Kawami M, Ojima T, Futatsugi S, Yumoto R, Takano M.
タイトル Role of plasminogen activator inhibitor-1 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells.
ジャーナル Biochem Biophys Res Commun
Abstract There is increasing evidence that epithelial-mesenchymal transition (EMT) contributes to the development of organ fibrosis. We demonstrated that methotrexate (MTX) clearly induced EMT through the transforming growth factor (TGF)-β-related signaling pathway in human alveolar epithelial cell line, A549. However, critical factors associated with MTX-induced EMT have not yet been identified. In our study, we attempted to identify factors playing a crucial role in MTX-induced EMT in A549 cells. We focused on plasminogen activator inhibitor-1 (PAI-1) as the possible target for the prevention of MTX-induced EMT-related lung injury. Comprehensive gene expression analysis by microarray revealed that mRNA expression level of PAI-1 was clearly increased by MTX treatment. In addition, using several cloned A549 cells, we found a good correlation between MTX-induced increase in mRNA expression levels of α-smooth muscle actin (SMA), a representative EMT marker, and PAI-1. Furthermore, MTX upregulated mRNA and protein expression levels of PAI-1 in A549 cells; this upregulation was canceled by co-treatment with SB431542, a TGF-β-related signaling pathway inhibitor. Notably, tiplaxtinin, a PAI-1 inhibitor, and knockdown of urokinase-type plasminogen activator receptor (uPAR) prevented MTX-induced EMT in A549 cells. These findings indicate that MTX may induce EMT via upregulation of PAI-1 expression and interaction of PAI-1 with uPAR in A549 cells.
巻・号 525(3)
ページ 543-548
公開日 2020-5-7
DOI 10.1016/j.bbrc.2020.02.131
PII S0006-291X(20)30412-5
PMID 32113686
MeSH A549 Cells Alveolar Epithelial Cells / drug effects Alveolar Epithelial Cells / metabolism* Epithelial-Mesenchymal Transition / drug effects* Gene Ontology Humans Methotrexate / pharmacology* Plasminogen Activator Inhibitor 1 / genetics Plasminogen Activator Inhibitor 1 / metabolism* RNA, Messenger / genetics RNA, Messenger / metabolism
IF 2.985
引用数 0
リソース情報
ヒト・動物細胞 A549