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Role of connexin hemichannels in the bladder outlet obstruction

Research Project

Project/Area Number 26462438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionUniversity of Yamanashi

Principal Investigator

KAMIYAMA Manabu  山梨大学, 総合研究部, 講師 (90362061)

Co-Investigator(Kenkyū-buntansha) 姚 建  山梨大学, 総合研究部, 准教授 (50303128)
Co-Investigator(Renkei-kenkyūsha) SAWADA Norifumi  山梨大学, 総合研究部, 講師 (70402055)
HANEDA Yaburu  山梨大学, 総合研究部, 助教 (20402068)
TAKEDA Masayuki  山梨大学, 総合研究部, 教授 (80197318)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膀胱 / ATP / ギャップ結合 / ヘミチャネル / 酸化ストレス / 機械的刺激 / 膀胱上皮細胞 / 膀胱炎 / 間質性膀胱炎 / チャネル / コネキシン43 / cyclophosphamide / connexin43
Outline of Final Research Achievements

This study is aimed to test the potential participation of connexin hemichannels in the control of bladder activity and pathological processes of bladder disorders. The results showed that mechanic stimulation of bladder with the increased volume of saline caused an abrupt release of ATP, which could be largely prevented by hemichannel inhibitors. In cultured urothelial cells, mechanical stimulation with glass beads or activation of TRPV4 channels with agonists caused a hemichannel-dependent release of ATP. Inhibition of hemichannels with CBX also largely prevented oxidative urothelial cells injury. In an in vivo mouse model of bladder cystitis induced by cyclophosphamide, CBX treatment attenuated bladder oxidative stress and inflammation, and improved bladder function. Our study suggests that connexin hemichannel might contribute to the regulation of bladder activity under both physiological and pathological conditions.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 Other

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (2 results) Remarks (1 results)

  • [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
    • Journal Title

      J Cell Mol Med

      Volume: 2017 Issue: 9 Pages: 346-346

    • DOI

      10.1111/jcmm.13100

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Connexin43 hemichannels contributes to the disassembly of cell junctions. through modulation of intracellular oxidative status2016

    • Author(s)
      Chi Y, Zhang X, Zhang Z, Mitsui T, Kamiyama M, Takeda M, Yao J.
    • Journal Title

      Redox Biol.

      Volume: 9 Pages: 198-209

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] AMPK Suppresses Connexin43 Expression in the Bladder and Ameliorates Voiding Dysfunction in Cyclophosphamide-induced Mouse Cystitis2016

    • Author(s)
      Zhang X, Yao J, Gao K, Chi Y, Mitsui T, Ihara T, Sawada N, Kamiyama M, Fan J, Takeda M
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 19708-19708

    • DOI

      10.1038/srep19708

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Suramin inhibits antibody binding to cell surface antigens and disrupts complement-mediated mesangial cell lysis.2016

    • Author(s)
      Piao H, Chi Y, Zhang X, Zhang Z, Gao K, Niimi M, Kamiyama M, Zhang J, Takeda M, Yao J
    • Journal Title

      J Pharmacy Sci.

      Volume: accepted Issue: 4 Pages: 224-234

    • DOI

      10.1016/j.jphs.2016.03.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Connexin43 channel contributes to TRPV4 activation-elicited oxidative cell injury.2016

    • Author(s)
      Xiling Zhang, Manabu Kamiyama, Zhen Zhang, Yanru Huang, Shan Gao, Xin Fang, Masayuki Takeda, Jian Yao.
    • Organizer
      第39会日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Pannexin channels contribute to air exposure-elicited oxidative injury in bronchial epithelial cells.2016

    • Author(s)
      Yanru Huang, Xiling Zhang, Zhen Zhang, Shan Gao, Xin Fang, Jian Yao.
    • Organizer
      第39会日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Remarks] 山梨大学 研究者総覧

    • URL

      http://erdb.yamanashi.ac.jp/rdb/A_DispInfo.Scholar/3_76/81EDF77BA86C42ED.html

    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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