Studies on intracellular and extracellular pathways involved in drug-induced pulmonary fibrosis
| Project/Area Number |
18K06749
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
Yumoto Ryoko 広島大学, 医系科学研究科(薬), 准教授 (70379915)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 薬剤誘発性肺線維症 / 上皮間葉転換(EMT) / 肺胞上皮Ⅱ型細胞 / 細胞周期の停止 / 細胞外分泌因子(PAI-1) / 肺線維症モデル動物 / 薬剤性肺線維症 / 上皮間葉転換 / 細胞外分泌因子 / PAI-1 / 肺胞上皮細胞 / ERストレス / ATF3/4 / 薬学 / 薬剤性肺障害 / 細胞周期停止 / サイトカイン / TGF-β1 / 上皮間葉転換 (EMT) / 細胞内経路 |
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| Outline of Final Research Achievements |
Several anticancer drugs including methotrexate (MTX) cause serious lung diseases such as pulmonary fibrosis. Although evidences showing the association of epithelial-mesenchymal transition (EMT) with pulmonary fibrosis are increasing, the mechanism underlying anticancer drug-induced EMT has been poorly understood.
In this research, we indicated that MTX-induced EMT may be related to cell cycle arrest in human alveolar epithelial cell line, A549. It was also suggested that the transforming growth factor (TGF)-β-related signaling pathway may partly be involved in MTX-induced EMT, and MTX may induce EMT via upregulation of ATF3 expression and increase of PAI-1 secretion followed by interaction of PAI-1 with uPAR
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| Academic Significance and Societal Importance of the Research Achievements |
薬剤性肺障害のうち、肺線維症は非常に重篤な障害であるが、その発症機構を細胞・分子レベルで解析した報告は乏しく、また有効な予防方法・治療方法はない。
本研究では薬剤誘発性EMTによる肺線維症に関わる分子機構を細胞内経路、細胞外経路の両面から解明することによって、肺線維症に対する新たな予防法や治療戦略を考案し得るところに学術的・社会的意義があると考える。
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Association of cell cycle arrest with anticancer drug-induced epithelial-mesenchymal transition in alveolar epithelial cells.2019
Author(s)
Kawami, M., Harada, R., Ojima, T., Yamagami, Y., Yumoto, R. and Takano, M.
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Journal Title
Toxicology
Volume: 424
Pages: 152231-152231
DOI
Related Report
Peer Reviewed
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[Journal Article] P-gp modulating effect of Azadirachta indica extract in multidrug-resistant cancer cell lines2018
Author(s)
Kawami, M., Yamada, Y., Issarachot, O., Junyaprasert, V. B., Yumoto, R., Takano, M.
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Journal Title
Pharmazie
Volume: 73
Pages: 104-109
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Functional expression of breast cancer resistance protein and cholesterol effect in human erythrocyte membranes2018
Author(s)
Takano, M., Higashi, M., Ito, H., Toyota, S., Hirabayashi, Y. and Yumoto, R.
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Journal Title
Pharmazie
Volume: 73
Pages: 700-705
Related Report
Peer Reviewed
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