論文

査読有り 国際誌
2020年7月

Nintedanib inhibits epithelial-mesenchymal transition in A549 alveolar epithelial cells through regulation of the TGF-β/Smad pathway.

Respiratory investigation
  • Hiroaki Ihara
  • Yoichiro Mitsuishi
  • Motoyasu Kato
  • Fumiyuki Takahashi
  • Ken Tajima
  • Takuo Hayashi
  • Moulid Hidayat
  • Wira Winardi
  • Aditya Wirawan
  • Daisuke Hayakawa
  • Koichiro Kanamori
  • Naohisa Matsumoto
  • Toshifumi Yae
  • Tadashi Sato
  • Shinichi Sasaki
  • Kazuya Takamochi
  • Yoshiyuki Suehara
  • Dai Ogura
  • Shin-Ichiro Niwa
  • Kenji Suzuki
  • Kazuhisa Takahashi
  • 全て表示

58
4
開始ページ
275
終了ページ
284
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.resinv.2020.01.003

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disorder. Recent studies have suggested that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells influences development of pulmonary fibrosis, which is mediated by transforming growth factor β (TGF-β). Tumor necrosis factor α (TNF-α), an important proinflammatory cytokine in IPF, has been shown to enhance TGF-β-induced EMT. Nintedanib, a multiple tyrosine kinase inhibitor that is currently used to treat IPF, has been shown to suppress EMT in various cancer cell lines. However, the mechanism of EMT inhibition by nintedanib and its effect on TGF-β and TNF-α signaling pathways in alveolar epithelial cells have not been fully elucidated. METHODS: A549 alveolar epithelial cells were stimulated with TGF-β2 and TNF-α, and the effects of nintedanib on global gene expression were evaluated using microarray analysis. Furthermore, Smad2/3 phosphorylation was assessed using western blotting. RESULTS: We found that in A549 cells, TGF-β2 and TNF-α treatment induces EMT, which was inhibited by nintedanib. Gene ontology analysis showed that nintedanib significantly attenuates the gene expression of EMT-related cellular pathways and the TGF-β signaling pathway, but not in the TNF-α-mediated signaling pathway. Furthermore, hierarchical cluster analysis revealed that EMT-related genes were attenuated in nintedanib-treated cells. Additionally, nintedanib was found to markedly suppress phosphorylation of Smad2/3. CONCLUSION: Nintedanib inhibits EMT by mediating EMT-related gene expression and the TGF-β/Smad pathway in A549 alveolar epithelial cells.

リンク情報
DOI
https://doi.org/10.1016/j.resinv.2020.01.003
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32359980
ID情報
  • DOI : 10.1016/j.resinv.2020.01.003
  • PubMed ID : 32359980

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