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The effects of epigenetic modification on the pathogenesis and the development of chronic kidney disease

Research Project

Project/Area Number 17H05061
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionThe University of Tokushima

Principal Investigator

MASUDA Masashi  徳島大学, 大学院医歯薬学研究部(医学域), 助教 (50754488)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
KeywordsFGF23 / 慢性腎臓病 / エピジェネティクス / エピゲノム変化
Outline of Final Research Achievements

In this study, we investigated the relationship between the increased plasma retinol levels in chronic kidney disease (CKD) and the epigenetic modification of fibroblast growth factor 23 (FGF23) gene. From the experiment of the administration of all-trans retinoic acid (ATRA) and retinoic acid receptor (RAR)-selective antagonists to CKD model mice, we suggested that ATRA may alleviate elevated plasma FGF23 levels through RARγ in CKD. In addition, lucifearase assay indicated that histone deacetylase (HDAC) may get involved in the depression effect of RA on the FGF23 gene promoter activity through RARγ.
Together, these results suggest that retinol may contribute to the alleviation of the abnormal elevation of plasma FGF23 levels in CKD.

Academic Significance and Societal Importance of the Research Achievements

わが国の慢性腎臓病(CKD)患者は年々増加傾向で、CKDは新たな「国民病」とも言われている。CKDになると腎臓でのリン調節機構の破綻による高リン血症や異常なFGF23の上昇が、骨病変・血管石灰化等の骨ミネラル代謝異常(CKD-MBD)や筋萎縮・脂肪減少等のタンパク質-エネルギー障害(CKD-PEW)への発展に寄与することが考えられている。本研究成果は、CKD発症・進行だけでなく、CKDに付随して起こる様々な障害の理解につながり、CKDの新規予防・治療法確立にとって大きな一歩となった。また、エピゲノム変化に関しては未だ不明な点が多く、本研究成果がエピゲノム研究発展の一助となることが期待される。

Report

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

    (15 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] University of Colorado(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] All-trans retinoic acid reduces the transcriptional regulation of intestinal sodium-dependent phosphate co-transporter gene (Npt2b).2020

    • Author(s)
      Masuda M, Yamamoto H, Takei Y, Nakahashi O, Adachi Y, Ohnishi K, Ohminami H, Yamanaka-Okumura H, Sakaue H, Miyazaki M, Takeda E, Taketani Y.
    • Journal Title

      The Biochemical journal.

      Volume: 477(4) Issue: 4 Pages: 817-831

    • DOI

      10.1042/bcj20190716

    • NAID

      120006980557

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reducition of stearoyl-CoA desaturase (SCD) contributes muscle atrophy through the excess endoplasmic reticulum stress in chronic kidney disease2020

    • Author(s)
      Yuki Niida、Masashi Masuda、Yuichiro Adachi、Aika Yoshizawa、Hirokazu Ohminami、Yuki Mori、Kohta Ohnishi、Hisami Yamanaka-Okumura、Takayuki Uchida、Takeshi Nikawa、Hironori Yamamoto、Makoto Miyazaki、Yutaka Taketani
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 慢性腎臓病による骨格筋の脂肪酸代謝異常を介した脂肪毒性(Liptoxicity)は筋委縮(サルコペニア) を惹起する2020

    • Author(s)
      新井田 裕樹, 増田 真志, 吉澤 和香, 足立 雄一郎, 大西 康太, 大南 博和, 内田 貴之, 奥村 仙示, 二川 健, 山本 浩範, 竹谷 豊
    • Organizer
      第23回日本病態栄養学会年次集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] レチノイン酸によるリポファジーを介した脂肪分解への影響2019

    • Author(s)
      森 優樹, 増田 真志, 吉田 里沙, 青柳 咲紀, 大西 康太, 大南 博和, 奥村 仙示, 二川 健, 濱田 広一郎, 竹谷 豊
    • Organizer
      第52回日本栄養・食糧学会 中国・四国支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] All-trans-retinoic-acid reduces intestinal phosphate uptake by the transcriptional regulation of sodium-dependent phosphate co-transporter gene (Npt2b)2019

    • Author(s)
      Masashi Masuda, Hironori Yamamoto, Adachi Yuichiro, Kohta Ohnishi, Hirokazu Ohminami, Hisami Okumura, Miyazaki Makoto, Eiji Takeda and Yutaka Taketani
    • Organizer
      ASBMR 2019 Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 慢性腎臓病モデルラットの骨格筋における脂肪酸代謝異常が及ぼす筋萎縮への影響2019

    • Author(s)
      新井田 裕樹, 増田 真志, 吉澤 和香, 足立 雄一郎, 大西 康太, 大南 博和, 内田 貴之, 奥村 仙示, 二川 健, 山本 浩範, 竹谷 豊
    • Organizer
      第66回日本栄養改善学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] All-trans retinoic acidによるヒストン修飾を介したFGF23発現への影響2019

    • Author(s)
      佐藤 景子, 増田 真志, 佐々木 晧平, 大南 博和, 大西 康太, 奥村 仙示, 山本 浩範, 竹谷 豊
    • Organizer
      第7回日本腎栄養代謝研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] レチノイン酸による小胞体ストレス感受性の影響2019

    • Author(s)
      足立 雄一郎, 増田 真志, 新井田 裕樹, 大西 康太, 内田 貴之, 奥村 仙示, 山本 浩範, 二川 健, 竹谷 豊
    • Organizer
      日本ビタミン学会第71回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] All-trans retinoic acidによるヒストン修飾を介したFGF23発現への影響2019

    • Author(s)
      佐藤 景子, 増田 真志, 足立 雄一郎, 大西 康太, 奥村 仙示, 山本 浩範, 竹谷 豊
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Hypervitaminosis A contributes to abnormal iron metabolism in chronic kidney disease2018

    • Author(s)
      Serina Kabutoya, Masashi Masuda, Yuichiro Adachi, Yilimulati Yimamu, Hisami Yamanaka-Okumura, Hironori Yamamoto, Yutaka Taketani
    • Organizer
      American Society of Nephrology Kidney Week 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sulforaphane induces lipolysis via lipophagy in mouse adipocyte2018

    • Author(s)
      Risa Yoshida, Masashi Masuda, Yuki Mori, Yuki Niida, Yuichiro Adachi, Kohta Ohnishi, Hisami Yamanaka-Okumura, Yoshichika Kawai, Yutaka Taketani
    • Organizer
      Kern Lipid Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小胞体ストレス応答誘導下におけるレチノイン酸の影響2018

    • Author(s)
      足立雄一郎、増田真志、新井田裕樹、大西康太、奥村仙示、竹谷豊
    • Organizer
      日本栄養・食糧学会 中国・四国支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨格筋脂質代謝異常が慢性腎臓病に伴うProtein Energy Wasting (CKD-PEW) を誘発する2017

    • Author(s)
      新井田裕樹、増田真志、吉澤和香、Ilimulati Yimamu、吉田里沙、甲谷芹奈、奥村仙示、河合慶親、竹谷豊、山本浩範
    • Organizer
      第71回 日本栄養・食糧学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Abnormal lipid metabolism in skeletal muscle mediates chronic kidney disease-induced sarcopenia2017

    • Author(s)
      Yuki Niida, Masashi Masuda, Aika Yoshizawa, Yuichiro Adachi, Yilimulati Yimamu, Serina Kabutoya, Risa Yoshida, Hisami Yamanaka-Okumura, Yoshichika Kawai, Makoto Miyazaki, Hironori Yamamoto, Yutaka Taketani
    • Organizer
      American Society of Nephrology Kidney Week 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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

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