A chronobiological approach to elucidate nocturia focusing on the urothelium

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H05682
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: University of Tsukuba (2018); Kyoto University (2015-2017)
• Principal Investigator: Negoro Hiromitsu 筑波大学, 附属病院, 病院講師 (80708595)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 排尿障害 / 時間生物学 / 尿路上皮 / コネキシン43 / Bmal1

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.

Free Research Field

排尿機能学、分子生物学、時間生物学

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。