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Discovery of aldosterone synthesis mechanisms and drug target via epigenomic regulation

Research Project

Project/Area Number 17H06894
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Endocrinology
Research InstitutionHiroshima University

Principal Investigator

KAZUHIRO KOBUKE  広島大学, 医系科学研究科(医), 寄附講座助教 (80805648)

Research Collaborator Itcho Kiyotaka  
Oki Kenji  
Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsエピゲノム調節 / アルドステロン / 副腎腫瘍 / 二次性高血圧 / アルドステロン産生腺腫 / 原発性アルドステロン症 / 循環器・高血圧 / 内科 / 内分泌性高血圧 / DNAメチル化
Outline of Final Research Achievements

This study reports a comprehensive integration analysis of DNA methylation and mRNA expression in APAs. We demonstrated that GPCR or GPCR-related genes had a much higher incidence of CpG island demethylation in APAs, and due to this demethylation, some receptors were in a state that would facilitate gene transcription. Also We showed that the PCP4 promoter was one of the most hypomethylated in APAs and that PCP4 transcription may be associated with demethylation as well as with CEBPA in APAs.
This study provides important information regarding the molecular mechanisms of ectopic or aberrant receptor expression in APAs and identifies therapeutic or diagnostic targets that could be studied further.

Academic Significance and Societal Importance of the Research Achievements

難治性の二次性高血圧および重症の動脈硬化性疾患の原因となりうる原発性アルドステロン症,なかでも重症となりうるアルドステロン産生腺腫について,その特異的なアルドステロンの過剰産生機構については未だ明らかでない部分が多いが,本研究により,DNAのメチル化を介した遺伝子発現調節機構の変化が,アルドステロン産生腺腫において重要な働きを担っていることが明らかとなった.アルドステロン合成制御機構の分子メカニズムについて詳細が明らかになることにより,新規分子標的治療薬や診断法の開発につながり,疾病の克服につながる.

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (3 results)

All 2018

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

  • [Journal Article] Aberrant G protein-receptor expression is associated with DNA methylation in aldosterone-producing adenoma2018

    • Author(s)
      Itcho K, Oki K, Kobuke K, Yoshii Y, Ohno H, Yoneda M, Hattori N.
    • Journal Title

      Mol Cell Endocrinol

      Volume: 461 Pages: 100-104

    • DOI

      10.1016/j.mce.2017.08.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Purkinje Cell Protein 4 Expression Is Associated With DNA Methylation Status in Aldosterone-Producing Adenoma.2018

    • Author(s)
      Kobuke K, Oki K, Gomez-Sanchez CE, Ohno H, Itcho K, Yoshii Y, Yoneda M, Hattori N.
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 103 Issue: 3 Pages: 965-971

    • DOI

      10.1210/jc.2017-01996

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] The regulation of PCP4 transcription via DNA methylation in aldosterone-producing adenoma2018

    • Author(s)
      Kiyotaka Itcho, Kenji Oki, Celso E, Gomez-Sanchez, Kazuhiro Kobuke, Yoko Yoshii, Haruya Ohno, Masayasu Yoneda
    • Organizer
      42nd Meeting of the International Aldosterone Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2017-08-25   Modified: 2020-03-30  

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