Establishment of a new alveolar epithelial cell model by gene transfection and its application to the study on drug transport and toxicity in the lungs
| Project/Area Number |
22390031
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Hiroshima University |
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Principal Investigator |
TAKANO Mikihisa 広島大学, 医歯薬保健学研究院(薬), 教授 (20211336)
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| Co-Investigator(Renkei-kenkyūsha) |
YUMOTO Ryoko 広島大学, 大学院・医歯薬保健学研究院, 助教 (70379915)
NAGAI Junya 広島大学, 大学院・医歯薬保健学研究院, 准教授 (20301301)
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| Project Period (FY) |
2010-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | 肺胞上皮細胞 / II型細胞モデル / Abca3遺伝子 / 薬剤性肺障害 / 上皮間葉転換 / 薬学 / モデル細胞作出 / ABCA3 / II型細胞 / ABCA3遺伝子 / 形質制御 / lamellar body / TGF-β1 / ブレオマイシン / 上皮間葉転移 / TGF-β_1 / アクチン骨格 / Abca3 / dipalmitoylphosphatidylcholine / 肺サーファクタント |
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| Research Abstract |
In order to develop a new alveolar type II epithelial cell model, Abca3 gene was introduced into RLE-6TN cells. Compared to RLE-6TN cells, the expression of Abca3 mRNA and the formation of lamellar bodies, characteristic intracellular organelle in type II cells, were increased in RLE/Abca3 cells. Surprisingly, the expression of other type II marker mRNAs and albumin uptake activity were also increased, indicating that introduction of Abca3 gene would direct RLE-6TN cells to more type II-like cells. In addition, RLE/Abca3 cells responded well to TGF-beta1 and bleomycin, compounds inducing epithelial-mesenchymal transition in alveolar epithelial cells, than RLE-6TN cells. Thus, RLE/Abca3 cells may be a promising in-vitro model system to analyze and predict drug-induced lung toxicity.
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Report
(5 results)
Research Products
(70 results)
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[Journal Article] Introduction of a single transporter gene ABCA3 directs RLE-6TN to more type II-like alveolar epithelial cells2013
Author(s)
Takano, M., Yamamoto, C., Sambuichi, K., Oda, K., Nagai, J., Shimamoto, A., Tahara, H. and Yumoto, R.
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Journal Title
Membrane
Volume: 38
Pages: 246-253
Related Report
Peer Reviewed
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[Journal Article] Introduction of a single transport gene ABCA3 directs RLE-6TN to more typeII-like alveolar epithelial cells.2013
Author(s)
Takano, M., Yamamoto, C., Sambuichi K., Oda, K., Nagai, J., Shimamoto, A., Tahara, H. and Yumoto, R
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Journal Title
Membrane
Volume: 38
Pages: 246-253
Related Report
Peer Reviewed
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[Journal Article] Endocytic Uptake of FITC-albumin by Human Alveolar Epithelial Cell Line A5492012
Author(s)
Yumoto, R., Suzuka, S., Oda, K., Imaoka, H. and Nagai, J. and Takano, M.
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Journal Title
Drug Metabolism and Pharmacokinetics
Volume: 27
Issue: 3
Pages: 336-343
DOI
NAID
ISSN
1347-4367, 1880-0920
Related Report
Peer Reviewed
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[Presentation] Effect of albumin-bound fatty acids on the expression of HIF-1-alpha and its target genes in the human renal tubular epithelial cell line2013
Author(s)
Yamamoto, A., Nagai, J., Toshimori, F., Katagiri, Y., Yumoto, R. and Takano, M.
Organizer
HK-2. 28th JSSX Annual Meeting in Tokyo
Place of Presentation
Tokyo
Related Report
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[Presentation] Expression and function of P-glycoprotein in alveolar epithelial cells and its modulation by cigarette smoke extract2013
Author(s)
Yumoto, R., Sasaki, Y., Horiuchi, T., Kato, Y., Kishimoto, U., Nagai, J. and Takano, M.
Place of Presentation
Dublin, Irland
Related Report
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[Presentation] Induction of phonotypical changes by transfection of a transporter gene Abca3 in cultured alveolar epithelial cell line RLE-6TN.2012
Author(s)
Yamamoto, C., Yumoto, R., Sambuichi, K., Oda, K., Nagai, J. and Takano, M.
Organizer
27th JSSX Annual Meeting in Tokyo
Place of Presentation
Tokyo
Related Report
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[Presentation] Effect of transfection of a transporter gene Abca3 on the phenotype of cultured alveolar epithelial cells.2012
Author(s)
Takano, M., Sambuichi, K., Yamamoto, C., Oda, K., Nagai, J. and Yumoto, R.
Organizer
18th North American Regional ISSX Meeting
Place of Presentation
Dallas, USA
Related Report
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