Analysis of molecular mechanism of drug-induced lung fibrosis and development of strategy to predict and prevent the fibrosis
Project/Area Number |
26293033
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | Hiroshima University |
Principal Investigator |
Takano Mikihisa 広島大学, 医歯薬保健学研究科(薬), 教授 (20211336)
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Co-Investigator(Renkei-kenkyūsha) |
YUMOTO Ryoko 広島大学, 大学院医歯薬保健学研究科, 准教授 (70379915)
KAWAMI Masashi 広島大学, 大学院医歯薬保健学研究科, 助教 (20725775)
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Research Collaborator |
Ehrhardt Carsten
Kim Kwang-Jin
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Project Period (FY) |
2014-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
|
Keywords | 薬剤性肺線維症 / 肺胞上皮Ⅱ型細胞 / 上皮間葉転換 / メトトレキサート / ブレオマイシン / マイクロRNA / ケルセチン / 薬学 / 肺線維症 / バイオマーカー |
Outline of Final Research Achievements |
Mechanisms underlying drug-induced pulmonary injury were investigated from the viewpoint of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells deeply related to pulmonary fibrosis. We have found that (1) drugs such as methotrexate act directly on alveolar epithelial cells to cause EMT, (2) various factors such as Smad2 phosphorylation, extracellular secretion factor, and microRNA are involved in the induction of EMT by drugs, (3) quercetin which is used as a supplement in Japan has been shown to have EMT inhibitory effect. These findings would be useful for understanding the molecular mechanisms of drug-induced lung injury and developing strategies for preventing pulmonary disorders.
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Report
(5 results)
Research Products
(97 results)
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[Journal Article] Effect of COA-Cl on transforming growth factor-β1-induced epithelial-mesenchymal transition in RLE/Abca3 cells.2017
Author(s)
Kawami, M., Deguchi, J., Yumoto, R., Sakakibara, N., Tsukamoto, I., Konishi,R., Takano, M.
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Journal Title
Drug Metabolism and Pharmacokinetics
Volume: 32
Pages: 224-227
NAID
Related Report
Peer Reviewed
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[Journal Article] Current progress toward a better understanding of drug disposition within the lungs: summary proceedings of the 1st Workshop on Drug Transporters in the Lungs.2017
Author(s)
Ehrhardt C, Beckman P, Couet W, Edwards C, Forbes B, Friden M, Gumbleton M, Hosoya KI, Kato Y, Nakanishi T, Takano M, Terasaki T, Yumoto R
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Journal Title
J Pharm Sci
Volume: 未定
Issue: 9
Pages: 2234-2244
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of Curcuma comosa extracts on the functions of peptide transporter and P-glycoprotein in intestinal epithelial cell.2017
Author(s)
Kawami, M., Yamada, Y., Toshimori, F., Issarachot, O., Junyaprasert, V.B., Yumoto, R., Takano, M.
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Journal Title
Pharmazie
Volume: 72
Pages: 123-127
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cobalt chloride induces expression and function of breast cancer resistance protein (BCRP/ABCG2) in human renal proximal tubular epithelial cell line HK-2.2017
Author(s)
Nishihashi, K., Kawashima, K., Nomura, T., Urakami-Takebayashi, Y., Miyazaki, M., Takano, M., Nagai, J.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 40
Issue: 4
Pages: 82-87
DOI
Related Report
Peer Reviewed
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[Journal Article] Methotrexate-induced epithelial-mesenchymal transition in the alveolar epithelial cell line A5492016
Author(s)
Kawami, M., Harabayashi, R., Miyamoto, M., Harada, R., Yumoto, R. and Takano, M.
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Journal Title
Lung
Volume: 194
Pages: 923-930
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Cisplatin resistance in human lung cancer cells is linked with dysregulation of cell cycle associated proteins.2015
Author(s)
Horibe S, Matsuda A, Tanahashi T, Inoue J, Kawauchi S, Mizuno S, Ueno M, Takahashi K, Maeda Y, Maegouchi T, Murakami Y, Yumoto R, Nagai J, Takano M.
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Journal Title
Life Sciences
Volume: 124
Pages: 31-40
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Modulation of P-glycoprotein function and multidrug resistance in cancer cells by Thai plant extracts.2014
Author(s)
Takano, M., Kakizoe, S., Kawami M., Nagai J., Patanasethanont, D., Sripanidkulchai B., Yumoto, R.
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Journal Title
Pharmazie
Volume: 69
Pages: 823-828
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Expression and function of a peptide transporter PEPT2 in alveolar epithelial cells in culture2014
Author(s)
Yumoto, R., Sugimoto, N., Sasaki, Y., Yamamoto, C., Nagai, J., Ehrhardt, C., Takano, M.
Organizer
The 5th FIP Pharmaceutical Sciences World Congress 2014
Place of Presentation
Melbourne (Australia)
Year and Date
2014-04-13 – 2014-04-16
Related Report