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Mechanisms for development of culprit lesions in primary aldosteronism that exhibits somatic mosaicism

Research Project

Project/Area Number 17K09890
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionKeio University

Principal Investigator

Mukai Kuniaki  慶應義塾大学, 医学部(信濃町), 講師 (80229913)

Co-Investigator(Kenkyū-buntansha) 西本 紘嗣郎  埼玉医科大学, 医学部, 准教授 (00365363)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルドステロン / ステロイドホルモン / 副腎 / 内分泌腫瘍 / 高血圧 / 体細胞変異
Outline of Final Research Achievements

This study aims at understanding the molecular basis for formation of culprit lesions of primary aldosteronism, which exhibits somatic mosaicism developed from a normal adrenal. Using a tumor-bearing adrenal, which was excised from a primary aldosteronism patient carrying a germline mutation of KCNJ5, an additional mutation was identified from the tumor portion but not from the nontumor portions. The result suggests that the secondary mutation caused the rapid growth of the tumor.

Academic Significance and Societal Importance of the Research Achievements

近年アルドステロン産生腺腫にイオンチャネル・ポンプ遺伝子群の体細胞変異が報告され病変形成への関与が示された。しかし、これらの遺伝子変異が腫瘍形成にどのように関与するのか不明であった。本研究では、ファーストヒットである変異を先天的に持った副腎にセカンドヒットとして体細胞変異が生じることにより腫瘍化することが示唆された。本成果は原発性アルドステロン症の病変形成機構の一端を示す。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Extension of Survival in Bilaterally Adrenalectomized Mice by Implantation of SF-1/Ad4BP-Induced Steroidogenic Cells2020

    • Author(s)
      Tanaka Tomoko, Aoyagi Chikao, Mukai Kuniaki, Nishimoto Koshiro, Kodama Shohta, Yanase Toshihiko
    • Journal Title

      Endocrinology

      Volume: 161 Issue: 3

    • DOI

      10.1210/endocr/bqaa007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ectopic adrenal adenoma causing gross hematuria: Steroidogenic enzyme profiling and literature review2019

    • Author(s)
      Ashikari Daisaku、Tawara So、Sato Katsuhiko、Mochida Junichi、Masuda Shinobu、Mukai Kuniaki、Turcu Adina、Nishimoto Koshiro、Yamaguchi Kenya、Takahashi Satoru
    • Journal Title

      IJU Case Reports

      Volume: - Issue: 3 Pages: 158-161

    • DOI

      10.1002/iju5.12068

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity2019

    • Author(s)
      Hayashi Taiki, Zhang Zhen, Al-Eyd Ghaith, Sasaki Atsushi, Yasuda Masanori, Oyama Masafumi, Gomez-Sanchez Celso E., Asakura Hirotaka, Seki Tsugio, Mukai Kuniaki, Nishimoto Koshiro
    • Journal Title

      The Journal of Steroid Biochemistry and Molecular Biology

      Volume: 191 Pages: 105361-105361

    • DOI

      10.1016/j.jsbmb.2019.04.010

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemistry for aldosterone synthase CYP11B2 and matrix-assisted laser desorption ionization imaging mass spectrometry for in-situ aldosterone detection2019

    • Author(s)
      Zhang Zhen、Sugiura Yuki、Mune Tomoatsu、Nishiyama Mitsuru、Terada Yoshio、Mukai Kuniaki、Nishimoto Koshiro
    • Journal Title

      Current Opinion in Nephrology and Hypertension

      Volume: 28 Issue: 2 Pages: 105-112

    • DOI

      10.1097/mnh.0000000000000487

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ステロイドホルモン合成の基礎とその制御2018

    • Author(s)
      向井邦晃
    • Journal Title

      臨床泌尿器科

      Volume: 72(6) Pages: 410-415

    • Related Report
      2018 Research-status Report
  • [Journal Article] Cortisol overproduction results from DNA methylation of CYP11B1 in hypercortisolemia2017

    • Author(s)
      Kometani, M., Yoneda, T., Demura, M., Koide, H., Nishimoto, K., Mukai, K., Gomez-Sanchez, C.E., Akagi, T., Yokota, T., Horike, S.I., Karashima, S., Miyamori, I., Yamagishi, M., Takeda, Y.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 11205-11205

    • DOI

      10.1038/s41598-017-11435-2

    • NAID

      120006460362

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel case of somatic KCNJ5 mutation in pediatric-onset aldosterone- producing adenoma2017

    • Author(s)
      Uchida N, Amano N, Yamaoka Y, Uematsu A, Sekine Y, Suzuki M, Watanabe J, Nishimoto K, Mukai K, Fukuzawa R, Hasegawa T, Ishii T
    • Journal Title

      J Endocrine Soc

      Volume: 1 Issue: 8 Pages: 1056-1061

    • DOI

      10.1210/js.2017-00210

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 原発性アルドステロン症の診療におけるアルドステロン合成酵素免疫染色法の意義2017

    • Author(s)
      西本紘嗣郎、林 泰樹、北村陽典、内田 厚、向井邦晃
    • Journal Title

      血圧

      Volume: 24 Pages: 861-968

    • Related Report
      2017 Research-status Report
  • [Presentation] Structural changes in the zona glomerulosa of normal aging adrenals2020

    • Author(s)
      van de Wiel, E.C.J., van Bonzel, L.G., Deinum, J., Mukai, K., Kusters, B., Langenhuijsen, J.H.
    • Organizer
      The 35th Annual European Association of Urology Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルドステロン合成酵素CYP11B2の発現は長命と逆相関する2019

    • Author(s)
      林 泰樹、Zhen Zhang、Ghaith AI-Eyd、佐々木惇、安田政実、小山政史、Celso E. Gomez-Sanchez、朝倉博孝、関 次男、向井邦晃、西本紘嗣郎
    • Organizer
      第31回日本内分泌外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] アルドステロン産生細胞クラスターの形成と進展2018

    • Author(s)
      向井邦晃、西本紘嗣郎、荻島正
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] New perioperative imaging techniques, immunohistochemistry and genetic analysis to investigate the feasibility of laparoscopic partial adrenalectomy in primary aldosteronism2018

    • Author(s)
      Van de Wiel E.C.J., Kusters B., Veltien A., Mann R., Mukai K., Deinum J., Langenhuijsen J.H.
    • Organizer
      The 36th World Congress of EndoUrology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Senescence associated decrease of aldosterone-producing cell cluster and incidental aldosterone-producing adenoma2018

    • Author(s)
      Hayashi, T., Zhen, Z., Aleyd, G., Sasaki, A., Yasuda, M., Oyama, M., Gomez-Sanchez, C., Asakura, H., Seki, T., Mukai, K., Nishimoto, K.
    • Organizer
      The 18th Conference on Adrenal Cortex
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] APCC Regresses and Incidental APA Appears with Senescence2018

    • Author(s)
      Hayashi, T., Zhang, Z., Al-Eyd, G., Sasaki, A., Yasuda, M., Oyama, M., Gomez-Sanchez, C.E., Asakura, H., Seki, T., Mukai, K., Nishimoto, K.
    • Organizer
      The 100th Endocrine Society Annual Meeting (ENDO 2018)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 内科学書 改訂第9版 vol.5 内分泌疾患 代謝・栄養疾患2019

    • Author(s)
      向井 邦晃(総編集 南学 正臣 部門編集 伊藤 裕、下村伊一郎)
    • Total Pages
      3672
    • Publisher
      中山書店
    • ISBN
      9784521747491
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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