Development of a model for the monitoring ontogenic expression of CYP3A by used of secreted reporter-expressing iPS cells
Project/Area Number |
25460195
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | University of Shizuoka (2015-2016) Tohoku Pharmaceutical University (2013-2014) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
永田 清 東北医科薬科大学, 薬学部, 教授 (80189133)
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Project Period (FY) |
2013-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | iPS細胞 / CYP3A4 / レポーター遺伝子 / 肝細胞 / 薬物代謝学 / CYP3A |
Outline of Final Research Achievements |
Human induced pluripotent stem cells (iPSCs) are a valuable source of hepatocytes for applications in drug development studies. Human CYP3A genes show unique expression changes, which are influenced by human development, and this developmental switch in expression between CYP3A4 and CYP3A7 genes occurs during the first 1 - 2 years after birth. In this study, based on the reproduction of the CYP3A expression pattern in the development, we aimed to establish methods for the differentiation of iPSCs into functional hepatocytes and evaluate novel transcriptional mechanism of pharmacokinetic-related genes. As results, we identified novel mechanisms involved in the induction of CYP3A4 and MRP3, and modified our previously established methods based on these results.
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Report
(5 results)
Research Products
(77 results)
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[Journal Article] Activation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid.2017
Author(s)
Abe, T., Takahashi, M., Kano, M., Amaike, Y., Ishii, C., Maeda, K., Kudoh, Y., Morishita, T., Hosaka, T., Sasaki, T., Kodama, S., Matsuzawa, A., Kojima, H., Yoshinari, K.
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Journal Title
Arch. Toxicol.
Volume: 印刷中
Issue: 6
Pages: 2365-2374
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Activation of p38 Mitogen-Activated Protein Kinase by Clotrimazole Induces Multidrug Resistance-Associated Protein 3 Activation through a Novel Transcriptional Element2016
Author(s)
Sasaki T, Inami K, Numata Y, Funakoshi K, Yoshida M, Kumagai T, Kanno S, Matsui S, Toriyabe T, Yamazoe Y, Yoshinari K, Nagata K
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Journal Title
J Pharmacol Exp Ther
Volume: 31
Issue: 1
Pages: 102-109
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers2016
Author(s)
Kumondai M, Hosono H, Orikasa K, Yoichi A, Sugimura H, Ozono S, Sugiyama T, Takayama T, Sasaki T, Hirasawa N, Hiratsuka M
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 39
Issue: 10
Pages: 1683-1686
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed
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[Journal Article] Genetic Polymorphisms of <i>CYP2A6</i> in a Case-Control Study on Bladder Cancer in Japanese Smokers2016
Author(s)
Kumondai M, Hosono H, Orikasa K, Yoichi A, Sugimura H, Ozono S, Sugiyama T, Takayama T, Sasaki T, Hirasawa N, Hiratsuka M
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 39
Issue: 1
Pages: 84-89
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed
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[Journal Article] Histone deacetylase inhibitor valproic acid promotes the differentiation of human induced pluripotent stem cells into hepatocyte-like cells.2014
Author(s)
Kondo Y, Iwao T, Yoshihashi S, Mimori K, Ogihara R, Nagata K, Kurose K, Saito M, Niwa T, Suzuki T, Miyata N, Ohmori S, Nakamura K, Matsunaga T.
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Journal Title
PLoS One.
Volume: 9
Issue: 8
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] 調剤薬局来局者を対象とした健康食品の使用実態調査とその情報に基づいたCYP2D6活性阻害評価2014
Author(s)
佐々木崇光, 熊谷 健, 佐々木瞳, 稲見敬太, 佐藤 裕, 髙橋昌悟, 松永民秀, 頭金正博, 細川正清, 大森 栄, 永田 清
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Journal Title
医療薬学
Volume: 40
Pages: 488-499
NAID
Related Report
Peer Reviewed
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[Journal Article] An Efficient Method for Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-like Cells Retaining Drug Metabolizing Activity2014
Author(s)
Kondo Y, Iwao T, Nakamura K, Sasaki T, Takahashi S, Kamada N, Matsubara T, Gonzalez FJ, Akutsu H, Miyagawa Y, Okita H, Kiyokawa N, Toyoda M, Umezawa A, Nagata K, Matsunaga T, Ohmori S
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Journal Title
Drug Metabolism and Pharmacokinetics
Volume: 29
Issue: 3
Pages: 237-243
DOI
NAID
ISSN
1347-4367, 1880-0920
Related Report
Peer Reviewed
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[Journal Article] Alteration of the function of the UDP-glucuronosyltransferase 1A subfamily by cytochrome P450 3A4: different susceptibility for UGT isoforms and UGT1A1/7 variants2014
Author(s)
Ishii Y, Koba H, Kinoshita K, Oizaki T, Iwamoto Y, Takeda S, Miyauchi Y, Nishimura Y, Egoshi N, Taura F, Morimoto S, Ikushiro S, Nagata K, Yamazoe Y, Mackenzie PI, Yamada H
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Journal Title
Drug Metabolism and Disposition
Volume: 42
Issue: 2
Pages: 229-238
DOI
Related Report
Peer Reviewed
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[Presentation] Profiles of immune cells and reproduction of immune-mediated drug-induced injury2015
Author(s)
Fujisaka Y, Kondo Y, Sasaki T, Kogure T, Inoue J, Nakagome Y, Wakui Y, Iwata T, Morosawa T, Umetu T, Suzuki H, Yamaguchi H, Mano N, Nagata K, Shimosegawa T
Organizer
American College of Gastroenterology 2015 annual scientific meeting
Place of Presentation
Honolulu
Year and Date
2015-10-16
Related Report
Int'l Joint Research
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[Presentation] Profiles of immune in peripheral blood and reproduction of immune-mediated drug-induced injury in vitro2015
Author(s)
Fujisaka Y, Kondo Y, Kogure T, Inoue J, Nakagome Y, Iwata T, Morosawa T, Umetu T, Suzuki H, Yamaguchi H, Sasaki T, Mano N, Nagata K, Shimosegawa T
Organizer
第19回日本肝臓学会
Place of Presentation
東京
Year and Date
2015-10-08
Related Report
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[Presentation] Pharmacokinetic function of hepatocyte-like cells differentiated from human iPS cells2013
Author(s)
Kondo Y, Iwao T, Ogihara R, Sasaki T, Nagata K, Kurose K, Horikawa T, Niwa T, Yamaori S, Ohmori S, Nakamura K, Matsunaga T
Organizer
28th JSSX annual meeting
Place of Presentation
Tokyo
Related Report
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[Presentation] Cytochrome P450 3A4 restores the catalytic property of udp-glucuronosyltransferase 1A1*6, one of the allelic variants which are concerned for causing gilbert syndrome2013
Author(s)
Kinoshita K, Oizaki T, Iwamoto Y, Nishimura Y, Miyauchi Y, Ikushiro S, Yamazoe Y, Nagata K, Mackenzie P, Yamada H, Ishii Y
Organizer
28th JSSX annual meeting
Place of Presentation
Tokyo
Related Report
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