Multi-hierarchical analysis of the role of TRPM4 subfamily members in cardiac atrial arrhythmogenicity
Project/Area Number |
15H04678
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | Fukuoka University |
Principal Investigator |
Inoue Ryuji 福岡大学, 医学部, 教授 (30232573)
|
Co-Investigator(Kenkyū-buntansha) |
沼田 朋大 福岡大学, 医学部, 講師 (20455223)
朱 欣 会津大学, コンピュータ理工学部, 上級准教授 (70448645)
|
Project Period (FY) |
2015-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
|
Keywords | 不整脈 / 生体ストレス / 心房リモデリング / 多階層シミュレーション / システム生理学 / TRPチャネル / 分子電気生理学 / TRPMチャネル |
Outline of Final Research Achievements |
Atrial fibrillation (Af) is a common arrhythmic disorder rapidly increasing in developed countries, and shows complex pathogenesis involving both structural and electrical remodeling that is frequently associated with other cardiac and metabolic/systemic diseases. This study aimed to comprehensively understand how stress-responsive molecules such as TRPM4 and TRPM7 channels can contribute to Af pathogenesis and some conduction disorders as well, by the combination of electrophysiological measurement and numerical simulation. The results, in particular, from cocultured cardiomyocyte/fibroblast monolayers and their equivalent 2D-model-based simulations suggested the critical importance of the synergy between excessive TRPM channel activity and fibroblast activation in promoting the arrhythmogenic processes.
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Academic Significance and Societal Importance of the Research Achievements |
近年、心房細動等の心リモデリング関連不整脈の研究領域では、心線維芽細胞の活性化やストレス応答分子TRPチャネルの発現・活性増加が新たな「基質」として注目を集めつつある。しかしこれまでは分子生物学的手法が主体であったため、その複雑な病態形成過程を統合的にとらえることは困難であった。本研究は、電気生理学実験と多階層の数理シミュレーションを融合させることで、心線維化とTRPM4チャネル過剰活性化の相乗的相互作用の重要性を定量的に示した点に意義がある。またこの研究で用いた手法は、ベンチトップレベルで遂行できることから、同分野の研究者コミュニティーに広く普及し今後の研究の進展に資することが期待される。
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Report
(5 results)
Research Products
(56 results)
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[Journal Article] SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation2020
Author(s)
Komatsu Shiho、Nomiyama Takashi、Numata Tomohiro、Kawanami Takako、Hamaguchi Yuriko、Iwaya Chikayo、Horikawa Tsuyoshi、Fujimura-Tanaka Yuki、Hamanoue Nobuya、Motonaga Ryoko、Tanabe Makito、Inoue Ryuji、Yanase Toshihiko、Kawanami Daiji
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Journal Title
Endocrine Journal
Volume: 67
Issue: 1
Pages: 99-106
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Integrative and theoretical research on the architecture of a biological system and its disorder2019
Author(s)
Shinichi Uchida, Yoshiyuki Asai, Yoshiaki Kariya, Kunichika Tsumoto, Hiroshi Hibino, Masashi Honma, Takeshi Abe, Fumiaki Nin, Yasutaka Kurata, Kazuharu Furutani, Hiroshi Suzuki, Hiroaki Kitano, Ryuji Inoue, Yoshihisa Kurachi
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Journal Title
The Journal of Physiological Sciences
Volume: 69
Issue: 3
Pages: 443-451
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction.2017
Author(s)
Michio Nakaya,Kenji Watari,Mitsuru Tajima,Takeo Nakaya,Shoichi Matsuda,Hiroki Ohara,Hiroaki Nishihara,Hiroshi Yamaguchi,Akiko Hashimoto,Mitsuho Nishida,Akiomi Nagasaka,Yuma Horii,Hiroki Ono,Gentaro Iribe,Ryuji Inoue,Makoto Tsuda,Kazuhide Inoue,Akira Tanaka,Masahiko Kuroda,Shigekazu Nagata,Hitoshi Kurose
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Journal Title
Journal of Clinical Investigation
Volume: 127
Issue: 1
Pages: 383-401
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds2016
Author(s)
S. Sawamura, M. Hatano, Y. Takada, K. Hino, T. Kawamura, J. Tanikawa, H. Nakagawa, H. Hase, A. Nakao, M. Hirano, R. Rotrattanadumrong, S. Kiyonaka, M.X. Mori, M. Nishida, Y. Hu, R. Inoue, R. Nagata and Y. Mori
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Journal Title
Mol Pharmacol
Volume: 89(3)
Issue: 3
Pages: 348-363
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Optical control of neuronal firing via photoinduced electron transfer in donor–acceptor conjugates2016
Author(s)
Yuta Takano, Tomohiro Numata, Kazuto Fujishima, Kazuaki Miyake, Kazuya Nakao, Wesley David Grove, Ryuji Inou, Mineko Kengaku, Shigeyoshi Sakaki, Yasuo Mori, Tatsuya Murakami and Hiroshi Imahori
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Journal Title
Chemical Science
Volume: n.d.
Issue: 5
Pages: 3331-3337
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Contribution of tyrosine kinase FYN to vascular remodeling in pulmonary arterial hypertension.2018
Author(s)
Hiraishi Keizo, Kurahara Lin, Zhang Ying, Yamamura Aya, Kishi Hiroko, Kobayashi Sei, Koga Kaori, Onitsuka Miki, Inoue Ryuji.
Organizer
3P-160. 30 March 2018, Takamatsu Tower Hall, Japan.
Related Report
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[Presentation] Electrophysiological and simulation analyses of atrial excitation/propagation in a co-cultured HL-1 cardiomyocytes-cardiac fibroblast monolayer.2017
Author(s)
Yaopeng Hu, Yanghua Shen, Keizo Hiraishi, Lin Kurahara, Jun Ichikawa, Tomohiro Numata, Wenfeng Shen, Xin Zhu, Ryuji Inoue.
Organizer
The 94th Annual Meeting of the Physiological Society of Japan
Place of Presentation
ACT CITY, Hamamatsu, Japan
Year and Date
2017-03-28
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