Study on mechanism of Notch signaling in testiculara germ cell and its clinical role in human
| Project/Area Number |
17K11198
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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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| Research Field |
Urology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 宏光 長崎国際大学, 薬学部, 准教授 (10263310)
福原 慎一郎 大阪大学, 医学系研究科, 講師 (20609870)
木内 寛 大阪大学, 医学系研究科, 講師 (70403053)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 男性不妊症 / 無精子症 / 遺伝子 / 男性不妊 / NKAP / 共役因子 / エクソン / シークエンス |
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| Outline of Final Research Achievements |
The Notch signaling pathway plays fundamental roles in diverse developmental processes through maintaining stem/progenitor cell populations and is the highly evolutionary conserved pathway that is initiated in response mainly to Notch ligands. Although Notch signaling also plays a critical role in germ cell development in Drosophila and Caenorhabditis elegans, its function and importance for spermatogenesis in mammals is controversial. Our study is to revealed a novel germ cell-specific gene Nkapl (NFkB activating protein-like) and Nakap (NFkB activating protein) is a functional nuclear protein as a repressor of Notch signaling in mice and an indispensable gene for spermatogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
NKAPおよびNKAPLの機能解析は、生殖細胞の特質を理解し、生殖細胞をin vitroで培養するために非常に重要な情報となる。将来的にES細胞を用いNKAPの解析を進めることによって、生殖細胞を能動的に分化させる遺伝子転写のカスケードを明らかにし、さらには、生殖細胞分化を支持する細胞を用いず、体細胞から容易に減数分裂に進める生殖細胞を誘導する系の構築が可能となる。さらに、男性不妊症におけるNKAP、NKAPL,およびNotchファミリー遺伝子の発現の関係と遺伝子多型の解析を進め、NOAの原因を追求し、Notchシグナリングを制御する低分子化合物の開発を通じて新規治療法の開発につなげうる。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Adipocyte GR Inhibits Healthy Adipose Expansion Through Multiple Mechanisms in Cushing Syndrome.2018
Author(s)
Hayashi R, Okuno Y, Mukai K, Kitamura T, Hayakawa T, Onodera T, Murata M, Fukuhara A, Imamura R, Miyagawa Y, Nonomura N, Otsuki M, Shimomura I.
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Journal Title
Endocrinology
Volume: 160
Issue: 3
Pages: 504-521
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intravesical ATP instillation induces urinary frequency because of activation of bladder afferent nerves without inflammatory changes in mice: A promising model for overactive bladder.2018
Author(s)
Ueda N, Kondo M, Takezawa K, Kiuchi H, Sekii Y, Inagaki Y, Soda T, Fukuhara S, Fujita K, Uemura M, Imamura R, Miyagawa Y, Nonomura N, Shimada S.
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Journal Title
Biochem Biophys Res Commun
Volume: 506
Issue: 3
Pages: 498-503
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Systematic characterization of human testis-specific actin capping protein β3 as a possible biomarker for male infertility.2017
Author(s)
Soda T, Miyagawa Y, Ueda N, Takezawa K, Okuda H, Fukuhara S, Fujita K, Kiuchi H, Uemura M, Okamoto Y, Tsujimura A, Tanaka H, Nonomura N.
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Journal Title
Hum Reprod.
Volume: 32
Pages: 514-522
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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