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2014 Fiscal Year Annual Research Report

PHSRNペプチドによる腹膜再生機構の薬理学的解明と臨床応用

Research Project

Project/Area Number 24591245
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

田村 雅仁  産業医科大学, 大学病院, 准教授 (40330980)

Co-Investigator(Kenkyū-buntansha) 芹野 良太  産業医科大学, 大学病院, 講師 (00309957)
宮本 哲  産業医科大学, 医学部, 非常勤医師 (30611305)
椛島 成利  産業医科大学, 大学病院, 非常勤医師 (80279322)
Project Period (FY) 2012-04-01 – 2015-03-31
Keywords腹膜透析 / 慢性腎不全 / 細胞接着
Outline of Annual Research Achievements

腹膜透析では透析液による腹膜劣化のため、長期間治療を継続することが困難である。腹膜劣化の原因として、透析液中に含まれる高糖濃度やブドウ糖分解代謝産物(GDPs)などの非生理的物質が考えられている。我々は培養腹膜中皮細胞において、透析液中に含まれるブドウ糖の濃度により、インテグリン依存性の細胞接着が阻害され、中皮細胞の創傷治癒が阻害されることを報告した(Tamura M, Kidney Int, 63: 722, 2003)。また、インテグリン活性化ペプチドであるPHSRNが腹膜中皮細胞の再生を促進させることを,
ラット腹膜透析モデルの両者において明らかにした(Miyamoto T, Tamura M, Nephrol Dial Transplant, 25: 1109, 2010)。この機序として、PHSRNはインテグリンによる細胞接着に中心的な働きをするFocal adhesion kinase (FAK)を活性化させ、細胞遊走能を向上させ創傷治癒を促進させることが明らかとなった。また、ブドウ糖に替わる浸透圧物質として開発されたIcodextrinでは、ブドウ糖のようなインテグリン依存性の細胞接着阻害作用がないことも明らかにした。本研究により腹膜透析における腹膜劣化の発症機序の解明や腹膜劣化進展の抑制について、インテグリンを介した創傷治癒が関与していることが明らかにされた。

  • Research Products

    (12 results)

All 2015 2014

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (3 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] A Novel UMOD Gene Mutation Associated with Uromodulin-associated Kidney Disease in a Young Woman with Moderate Kidney Dysfunction.2015

    • Author(s)
      Kuma A, Tamura M, Ishimatsu N, Miyamoto T, Serino R, Ishimori S, Morisada N, Iijima K, Yamada S, Takeuchi M, Abe H, Otsuji Y.
    • Journal Title

      Intern Med

      Volume: 54(6) Pages: 631-5

    • DOI

      10.2169/internalmedicine

    • Peer Reviewed / Open Access
  • [Journal Article] Coronary plaque progression of non-culprit lesions after culprit percutaneous coronary intervention in patients with moderate to advanced chronic kidney disease: intravascular ultrasound and integrated backscatter intravascular ultrasound study.2015

    • Author(s)
      Kashiyama K, Sonoda S, Muraoka Y, Suzuki Y, Kamezaki F, Tsuda Y, Araki M, Tamura M, Takeuchi M, Abe H, Okazaki M, Fujino Y, Otsuji Y.
    • Journal Title

      Int J Cardiovasc Imaging.

      Volume: in press Pages: in press

    • Peer Reviewed
  • [Journal Article] Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice.2014

    • Author(s)
      Tsutsui M, Tanimoto A, Tamura M, Mukae H, Yanagihara N, Shimokawa H, Otsuji Y.
    • Journal Title

      J Pharmacol Sci.

      Volume: 127(1) Pages: 42-52

    • DOI

      10.1016/j.jphs.2014.10.002.

    • Peer Reviewed
  • [Journal Article] Pacing and sensing interference by air bubble surrounding the non-extended helix of intact active fixation lead.2014

    • Author(s)
      Oginosawa Y, Abe H, Ohe H, Hayashi K, Kohno R, Watabe T, Takahashi M, Fujino Y, Tamura M, Takeuchi M, Otsuji Y.
    • Journal Title

      Circ J

      Volume: 78(12) Pages: 2862-6

    • Peer Reviewed
  • [Journal Article] Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse.2014

    • Author(s)
      Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Arakaki K, Kina-Tanada M, Kubota H, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Igarashi T, Ueno S, Matsushita M, Ishiuchi S, Masuzaki H, Ohya Y, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M.
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 77 Pages: 29-41

    • DOI

      10.1016/j.yjmcc.2014.09.021.

    • Peer Reviewed
  • [Journal Article] Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.2014

    • Author(s)
      Kuma A, Yamada S, Wang KY, Kitamura N, Yamaguchi T, Iwai Y, Izumi H, Tamura M, Otsuji Y, Kohno K.
    • Journal Title

      PLoS One

      Volume: 9(7) Pages: e103240

    • DOI

      10.1371/journal.pone.0103240.

    • Peer Reviewed / Open Access
  • [Journal Article] Atrial pacing site and atrioventricular conduction in patients paced for sinus node disease.2014

    • Author(s)
      Watabe T, Abe H, Kohno R, Oginosawa Y, Hayashi K, Ohe H, Tamura M, Takeuchi M, Otsuji Y.
    • Journal Title

      J Cardiovasc Electrophysiol.

      Volume: 25(11) Pages: 1224-31

    • DOI

      10.1111/jce.12476

    • Peer Reviewed
  • [Journal Article] Aortic root geometry in patients with aortic stenosis assessed by real-time three-dimensional transesophageal echocardiography.2014

    • Author(s)
      Wu VC, Kaku K, Takeuchi M, Otani K, Yoshitani H, Tamura M, Abe H, Lin FC, Otsuji Y.
    • Journal Title

      J Am Soc Echocardiogr.

      Volume: 27(1) Pages: 32-41

    • DOI

      10.1016/j.echo.2013.10.007.

    • Peer Reviewed
  • [Presentation] Induction of Kidney Fibrosis by Fibronectin Synthesis via WNT Signaling2014

    • Author(s)
      Kuma A, Tamura M
    • Organizer
      The 2014 American Society for Cell Biology Meeting
    • Place of Presentation
      Philadelphia (USA)
    • Year and Date
      2014-12-07 – 2014-12-07
  • [Presentation] 腹膜線維化の分子機序2014

    • Author(s)
      Tamura M
    • Organizer
      第57回日本腎臓学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川、横浜)
    • Year and Date
      2014-07-04 – 2014-07-04
  • [Presentation] Biocompatibility and Efficacy of Icodextrin2014

    • Author(s)
      Tamura M
    • Organizer
      7th Congress of the International Society for Hemodialysis
    • Place of Presentation
      Okinawa Convention Center (Okinawa, Ginowan)
    • Year and Date
      2014-04-27 – 2014-04-27
    • Invited
  • [Book] 全人力・科学力・透析力・for the people 透析医学2014

    • Author(s)
      田村雅仁、宮本哲、芹野良太
    • Total Pages
      720 (165-169)
    • Publisher
      医薬ジャーナル社

URL: 

Published: 2016-06-01  

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