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Effects of pericyte-specific ATP-dependent potassium channel on cardiac function

Research Project

Project/Area Number 19K23835
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0802:Biomedical structure and function and related fields
Research InstitutionNippon Medical School

Principal Investigator

Ando Koji  日本医科大学, 先端医学研究所, 講師 (10736010)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsペリサイト / Kcnj8 / Abcc9 / K-ATPチャネル
Outline of Research at the Start

本研究では、毛細血管支持細胞であるペリサイト特異的に発現することを見出したKCNJ8およびABCC9複合体から為るATP依存性カリウムチャネルの心臓における機能解析を実施する。特に『ペリサイトにおけるATP依存性カリウムチャネルの機能異常が心疾患を誘発する』という仮説を検証することにより、ペリサイトによる心機能調節機構の分子基盤を明らかにし、疾患の発症機構の解明と治療法開発を目指した研究に挑む。

Outline of Final Research Achievements

In this study, we found that the K-ATP channel functions with the onset of ABCC9/KCNJ8 expression in the pericytes from the early developmental stage. While inhibition of K-ATP channel was converted to the elevation of intracellular Ca2 +, transient activation of the K-ATP channel in the resting condition unexpectedly caused little Ca2 + changes. Using the experimental model developed in this study, we are now able to analyze Ca2 + kinetics and gene expression changes in the Kcnj8 or Abcc9 mutants, and analyze the association between pericyte intracellular Ca2 + fluctuations and heart disease. On the other hand, we found the change in Kcnj8 gene expression along the development in the mouse heart. In the early developmental mouse heart, Kcnj8 was also expressed in epicardial cells, implying the possibility of a new mechanism other than the hypothesis that pericyte abnormalities that were initially predicted cause heart disease.

Academic Significance and Societal Importance of the Research Achievements

心疾患は死因の主要な原因であることから、心臓におけるペリサイト機能解析は学術的側面に加え、臨床面でも重要な課題の一つであると言える。ペリサイト特異的ATP依存性カリウムチャネル異常が心疾患を誘発するメカニズムは十分には分かっておらず、本研究によりKcnj8遺伝子の発現変化とペリサイトにおけるK-ATPチャネルと細胞内Ca2+濃度の連関を明らかに出来たことは、今後の詳細なK-ATPチャネルの役割およびその異常により誘発される心疾患の発症機構の理解に貢献するものと考えられる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (5 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Uppsala university/Karolinska Institute(スウェーデン)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Univ. Massachusetts Medical School(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Uppsala university(スウェーデン)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Protocol for analysis of integrin-mediated cell adhesion of lateral plate mesoderm cells isolated from zebrafish embryos2021

    • Author(s)
      Rho Seung-Sik、Oguri-Nakamura Eri、Ando Koji、Yamamoto Kiyotake、Takagi Yuki、Fukuhara Shigetomo
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 2 Pages: 100428-100428

    • DOI

      10.1016/j.xpro.2021.100428

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conserved and context-dependent roles for Pdgfrb signaling during zebrafish vascular mural cell development2021

    • Author(s)
      Ando Koji、Shih Yu-Huan、Ebarasi Lwaki、Grosse Ann、Portman Daneal、Chiba Ayano、Mattonet Kenny、Gerri Claudia、Stainier Didier Y.R.、Mochizuki Naoki、Fukuhara Shigetomo、Betsholtz Christer、Lawson Nathan D.
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2021.03.29.437552

    • Related Report
      2020 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Rap1b promotes Notch signal-mediated hematopoietic stem cell development by enhancing integrin-mediated cell adhesion.2019

    • Author(s)
      Rho S., Kobayashi I., Oguri-Nakamura E., Ando K., Fujiwara M., Kamimura N., Hirata H., Iida A., Iwai Y., Mochizuki N., Fukuhara S.
    • Journal Title

      Developmental Cell

      Volume: 印刷中 Issue: 5 Pages: 1-16

    • DOI

      10.1016/j.devcel.2019.03.023

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Investigation of the molecular mechanism underlying mural cell specification in zebrafish2021

    • Author(s)
      安藤 康史 、福原 茂朋
    • Organizer
      第28回日本血管生物医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Roles of pericytes in wound angiogenesis clarified by live imaging of adult zebrafish2021

    • Author(s)
      石井智裕,弓削進弥,野一色千景,安藤康史,望月直樹,福原茂朋
    • Organizer
      第28回日本血管生物医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ペリサイトによる血管新生制御機構の解明2020

    • Author(s)
      石井智裕,弓削進弥,安藤康史,福原茂朋.
    • Organizer
      第6回 日本血管生物医学若手研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血管壁細胞のspecificationに関わるシグナル機構2019

    • Author(s)
      安藤 康史
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ATP依存性カリウムチャネルによる血管平滑筋細胞分化調節2019

    • Author(s)
      安藤 康史
    • Organizer
      第27回日本血管生物医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Book] 血管新生 -基礎と臨床-2019

    • Author(s)
      安藤 康史
    • Total Pages
      120
    • Publisher
      医学のあゆみ
    • Related Report
      2019 Research-status Report
  • [Remarks] http://www.nmsbyoutai.com/

    • Related Report
      2019 Research-status Report

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Published: 2019-09-03   Modified: 2022-01-27  

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