A chronobiological approach to elucidate nocturia focusing on the urothelium
| Project/Area Number |
15H05682
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | University of Tsukuba (2018)
Kyoto University (2015-2017) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Keywords | 排尿障害 / 時間生物学 / 尿路上皮 / コネキシン43 / Bmal1 / 時計遺伝子 / ATP / コネキシン４３ / コネキシン / 概日リズム |
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| Outline of Final Research Achievements |
We have found that a functional circadian rhythm exists in the urothelium, and it coordinates connexin43 (Cx43) expression and function as hemichannels that provide a direct pathway of ATP release for mechanotransduction and signaling in the urothelium. In addition, we have generated conditional knockout C57BL/6 mice lacking a major clock gene Bmal1 or Cx43 in the urothelium only. Furthermore, we have generated P(Bmal1)-dLuc reporter cell lines derived from immortalized human urothelial cells and have identified a few candidate compounds that could modify the circadian rhythm of the urothelium.
We presently progress the research to investigate the role of peripheral clock in the urothelium for the bladder function and diseases characterized as disorders of micturition rhythm including nocturnal enuresis and nocturia.
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| Academic Significance and Societal Importance of the Research Achievements |
膀胱は夜間にしっかりと尿を溜め、日中はしっかり排尿するようにその機能の日内変動を有し、個体の生命活動をサポートしている。膀胱機能の昼夜差の形成メカニズムを解明することは、夜間頻尿や夜尿症など、排尿の昼夜差が乱れた疾患の機序解明に貢献すると考えられる。本研究から、尿路上皮でのCx43の発現や機能を制御すること、それに伴うATP放出を制御すること、概日時計に作用することをターゲットとした薬剤が夜間頻尿や夜尿症の新たな治療薬の候補となることが期待される。
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Report
(5 results)
Research Products
(41 results)
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[Journal Article] <b>Circadian rhythms of micturition during jet </b><b>lag </b>2018
Author(s)
Ito K, Yasuda M, Maeda Y, Fustin JM, Yamaguchi Y, Kono Y, Negoro H, Kanematsu A, Ogawa O, Doi M, and Okamura H
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Journal Title
Biomedical Research
Volume: 39
Issue: 2
Pages: 57-63
DOI
NAID
ISSN
0388-6107, 1880-313X
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Circadian coordination of ATP release in the urothelium via connexin43 hemichannels2018
Author(s)
Sengiku A, Ueda M, Kono J, Sano T, Nishikawa N, Kunisue S, Tsujihana K, Liou L, Kanematsu A, Shimba S, Doi M, Okamura H, Ogawa O, and Negoro H
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Journal Title
Sci. Rep.
Volume: 8
Issue: 1
Pages: 1996-1996
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dietary Sodium Restriction Reduces Nocturnal Urine Volume and Nocturnal Polyuria Index in Renal Allograft Recipients With Nocturnal Polyuria.2017
Author(s)
Okumura Y, Asai K, Kobayashi T, Miyata H, Tanaka Y, Okada Y, Sakai K, Kamba T, Tsuji H, Shide K, Nagashima K, Yanagita M, Inagaki N, Ogawa O, Negoro H
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Journal Title
Urology
Volume: 106
Pages: 60-64
Related Report
Peer Reviewed
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[Presentation] The circadian rhythm coordinates the ATP release in the urothelium via the connexin43 hemichannel2017
Author(s)
Atsushi Sengiku, Hiromitsu Negoro, Takeshi Sano, Masakatsu Ueda, Jin Kono, Kyoto, Japan, Louis Liou, Cambridge, MA, Hitoshi Okamura, Osamu Ogawa
Organizer
AUA 2017 Annual Meeting
Related Report
Int'l Joint Research
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