| Project/Area Number |
23390381
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
TAKEDA Masayuki 山梨大学, 医学工学総合研究部, 教授 (80197318)
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| Co-Investigator(Kenkyū-buntansha) |
TOMINAGA Makoto 大学共同利用機関法人自然科学研究機構, 細胞生理部門, 教授 (90260041)
KOIZUMI Syuichi 山梨大学, 医学工学総合研究部, 教授 (10280752)
MOCHIDUKI Tsutomu 山梨大学, 医学工学総合研究部, 医学研究員 (50377496)
MIYAMOTO Tatsuya 山梨大学, 医学部附属病院, 助教 (80456459)
芳山 充晴 山梨大学, 医学工学総合研究部, 教授 (20422694)
荒木 勇雄 滋賀医科大学, 医学部, 准教授 (50252424)
小林 英樹 山梨大学, 医学工学総合研究部, 助教 (50402053)
座光寺 秀典 山梨大学, 医学工学総合研究部, 講師 (60345717)
澤田 智史 山梨大学, 医学部附属病院, 助教 (70402055)
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAGOMI Hiroshi 山梨大学, 医学工学総合研究部, 助教 (80418714)
KIRA Satoru 山梨大学, 医学部附属病院, 病院助教 (10530115)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
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| Keywords | Afferent nerve / Urinary bladder / Overactive bladder / イオンチャネル / TRP / VNUT / PIEZO / P2Y6 / ATP / Piezo1 / メカノセンサー / 膀胱 / 尿路上皮 |
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| Research Abstract |
We performed a systematic analysis of the molecular and functional expression of Piezo1 channels in the urothelium.
Immunofluorescence examination demonstrated abundant expression of Piezo1 in the mouse and human urothelium. Urothelial cells isolated from mice exhibited a Piezo1-dependent increase in cytosolic Ca2+ concentrations in response to mechanical stretch stimuli, leading to potent ATP release; this response was suppressed in Piezo1- knockdown cells. In addition, Piezo1 and TRPV4 distinguished different intensities of mechanical stimulus.
Moreover, GsMTx4, an inhibitor of stretch-activated channels, attenuated the Ca2+ influx into urothelial cells and decreased ATP release from them upon stretch stimulation. These results suggest that Piezo1 senses extension of the bladder urothelium, leading to production of an ATP signal. Thus, inhibition of Piezo1 might provide a promising means of treating bladder dysfunction.
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