Role of TRPV4/Connexin/Pannexin Interaction in Bladder Cystitis
Project/Area Number |
17K11176
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Urology
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Research Institution | University of Yamanashi |
Principal Investigator |
YAO Jian 山梨大学, 大学院総合研究部, 准教授 (50303128)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | TRPV4 / Connexin43 / 膀胱 / 間質性膀胱炎 / 酸化ストレス / インフラマソーム活性化 / 相互作用 / Cx43 / 間質膀胱炎 / inflammasome / NADPH oxidase / チャネル / TXNIP / シクロホスファミド / コネクシン / 免疫染色 / パネキシン |
Outline of Final Research Achievements |
TRPV4 and Cx43 channels are involved in the control of bladder contractile response. Blockade of each of them attenuates bladder overactivity in cyclophosphamide (CYP)-induced cystitis. It is unclear why two different channels similarly regulate bladder activity. We speculated that there existed a close interaction between TRPV4 and Cx43 channels under pathological situations, which contributed to the initiation and development of bladder abnormality. The aim of this study was to test this hypothesis.In a mouse model of CYP cystitis, TRPV4 and Cx43 proteins were found to be markedly increased. Further analysis revealed that the interaction between TRPV4 and Cx43 channels contributed to the regulation of the intracellular redox status and inflammasome activation. Collectively, our study indicates that the interaction between TRPV4 and Cx43 underlies the bladder abnormality through mechanisms involving its actions on the intracellular oxidative status and inflammatory response.
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Academic Significance and Societal Importance of the Research Achievements |
間質性膀胱炎とは、原因不明で、頻尿・尿意亢進・膀胱痛などの症状を呈する疾患である。患者の生活の質は膀胱刺激症状により大きく損なわれる。そのため、病態発症機序の解明、治療法の開発が望まれている。我々は、TRPV4及びCx43チャネルは膀胱の機能調節に重要であることから、両チャネル間の相互作用は膀胱炎の進展に寄与していることを想定し、研究を行った。動物及び細胞モデルにおいてTRPV4及びCx43チャネル間に緊密な相互作用が存在すること、また酸化ストレス及び炎症反応を調節していることを明らかにした。以上からTRPV4とCx43チャネル間の相互作用を標的とする治療法が有効であることを示している。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Carbenoxolone inhibits TRPV4 channel-initiated oxidative urothelial injury and ameliorates cyclophosphamide-induced bladder dysfunction2017
Author(s)
Zhang X,Gao S,Tanaka M,Zhanq Z,Huanq Y,Mitsui T,Kamiyama M,Koizumi S,Fan J,Takeda M,Yao J
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Journal Title
J Cell Mol Med
Volume: 2017
Issue: 9
Pages: 346-346
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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