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Association of podocyte DNA damage and epigenetic alterations with renal aging

Research Project

Project/Area Number 19K08688
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionKeio University

Principal Investigator

Hayashi Kaori  慶應義塾大学, 医学部(信濃町), 講師 (60445294)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsポドサイト / DNA損傷 / エピゲノム / DNAメチル化 / 老化 / DNA損傷修復 / 慢性腎臓病 / 腎老化 / エピゲノム変化
Outline of Research at the Start

申請者がこれまで腎糸球体ポドサイトを中心に検討し報告してきた、腎臓エピゲノム変化と慢性腎臓病(CKD)との関連を示唆する結果(JCI 2014, Kidney Int 2015)、およびそれらエピゲノム変化とDNA損傷修復環境との関連性を示唆する最近の研究成果に基づき(Cell Rep 2019)、本研究では、腎老化および腎老化をベースとして発症するCKDの病態における、ポドサイトのDSBおよびエピゲノム変化の役割を、ポドサイト特異的DSB誘導マウスおよび腎生検検体を用いた検討により明らかにするものである。

Outline of Final Research Achievements

This study revealed that podocyte DNA damage caused altered DNA methylation, which induced sustained changes in podocyte phenotypes and contributed pathogenesis of kidney diseases. Clinical studies suggested that podocyte DNA damage and DNA methylation, evaluated using renal biopsy samples or urine-derived cells, may be potential markers for predicting renal prognosis.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会を背景とした、高血圧や糖尿病増加に伴う慢性腎臓病(CKD)が増加していることから、老化に伴う変化を理解することは重要である。老化の本質として、DNA損傷やエピゲノム変化の蓄積が重要であることが知られており、本研究では腎臓の老化を理解するためにポドサイトDNA損傷や随伴するエピゲノム変化について検討した。その結果、ポドサイトDNA損傷は、老化のみならず多くのCKDに共通して認められる現象であり、新規治療標的、予後予測マーカーとして有用である可能性が明らかになった。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Altered DNA methylation in kidney disease: Useful markers and therapeutic targets.2022

    • Author(s)
      Kaori Hayashi
    • Journal Title

      Clin Exp Nephrol

      Volume: 26(4) Issue: 4 Pages: 309-315

    • DOI

      10.1007/s10157-022-02181-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation2021

    • Author(s)
      Akihito Hishikawa, Kaori Hayashi (corresponding author), Akiko Kubo, Kazutoshi Miyashita, Akinori Hashiguchi, Kenichiro Kinouchi, Norifumi Yoshimoto, Ran Nakamichi, Riki Akashio, Erina Sugita, Tatsuhiko Azegami, Toshiaki Monkawa, Makoto Suematsu, Hiroshi Itoh.
    • Journal Title

      iScience.

      Volume: 24(12) Issue: 12 Pages: 103436-103436

    • DOI

      10.1016/j.isci.2021.103436

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic alterations in podocytes in diabetic nephropathy.2021

    • Author(s)
      Sugita E, Hayashi K (corresponding author), Hishikawa A, Itoh H.
    • Journal Title

      Front Pharmacol,

      Volume: 12 Pages: 759299-759299

    • DOI

      10.3389/fphar.2021.759299

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vaccination against receptor for advanced glycation end products attenuates the progression of diabetic kidney disease.2021

    • Author(s)
      Azegami T, Nakayama T, Hayashi K, Hishikawa A, Yoshimoto N, Nakamichi R, Itoh H.
    • Journal Title

      Diabetes.

      Volume: 70(9) Issue: 9 Pages: 2147-2158

    • DOI

      10.2337/db20-1257

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of high glucose and lipotoxicity on diabetic podocytes2021

    • Author(s)
      Ran Nakamichi, Kaori Hayashi, Hiroshi Itoh
    • Journal Title

      Nutrients

      Volume: 13(1) Issue: 1 Pages: 241-241

    • DOI

      10.3390/nu13010241

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA damage and expression of DNA methylation modulators in urine-derived cells of patients with hypertension and diabetes2020

    • Author(s)
      Hishikawa Akihito、Hayashi Kaori、Yoshimoto Norifumi、Nakamichi Ran、Homma Koichiro、Itoh Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-60420-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy2020

    • Author(s)
      Hayashi Kaori、Hishikawa Akihito、Hashiguchi Akinori、Azegami Tatsuhiko、Yoshimoto Norifumi、Nakamichi Ran、Tokuyama Hirobumi、Itoh Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-019-57140-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Damage Repair and DNA Methylation in the Kidney2019

    • Author(s)
      Hayashi Kaori、Hishikawa Akihito、Itoh Hiroshi
    • Journal Title

      American Journal of Nephrology

      Volume: 50 Issue: 2 Pages: 81-91

    • DOI

      10.1159/000501356

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes2019

    • Author(s)
      Hishikawa Akihito、Hayashi Kaori、Abe Takaya、Kaneko Mari、Yokoi Hideki、Azegami Tatsuhiko、Nakamura Mari、Yoshimoto Norifumi、Kanda Takeshi、Sakamaki Yusuke、Itoh Hiroshi
    • Journal Title

      Cell Reports

      Volume: 26 Issue: 5 Pages: 1318-1332

    • DOI

      10.1016/j.celrep.2019.01.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] DNA damage repair and altered epigenome in the kidney: as useful markers and therapeutic targets2021

    • Author(s)
      Kaori Hayashi
    • Organizer
      第64回日本腎臓学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Continuous non-mutagenic DNA damage in podocytes activates inflammatory response and may accelerate kidney aging2021

    • Author(s)
      Ran Nakamichi, Akihito Hishikawa, Kaori Hayashi, Toshiaki Monkawa, Hiroshi Itoh
    • Organizer
      ASN Kidney Week
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖尿病腎症とエピゲノム~ポドサイトにおけるKAT5発現とDNAメチレーション2020

    • Author(s)
      林 香
    • Organizer
      第63回日本糖尿病学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ポドサイトにおけるDNA損傷2020

    • Author(s)
      林 香
    • Organizer
      第93回日本内分泌学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] AKIプレコンディショニング効果におけるDNA修復因子KAT5の役割の検討2020

    • Author(s)
      菱川彰人 林 香 他
    • Organizer
      第63回日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] DNA repair factor KAT5 acts against ischemia-reperfusion injury through promoted DNA repair and KCC3-dependent TGF regulation in proximal tubular cells2020

    • Author(s)
      Akihito Hishikawa, Kaori Hayashi, et al.
    • Organizer
      ASN Kidney Week 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of DNA repair factor KAT5 and DNA methylation modulators in urinary shedding cells of patients with diabetic kidney disease2019

    • Author(s)
      Akihito Hishikawa, Kaori Hayashi, Hiroshi Itoh
    • Organizer
      ASN Kidney Week 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA修復因子KAT5を介したエピゲノム調節機構はポドサイトの形質維持に必須であり、糖尿病性腎症新規治療標的となり得る2019

    • Author(s)
      菱川彰人、林 香、中村真理、畔上達彦、吉本憲史、伊藤裕
    • Organizer
      内分泌学会総会(YIA受賞)
    • Related Report
      2019 Research-status Report
  • [Presentation] 腎糸球体ポドサイトにおけるDNA修復因子KAT5の発現低下はDNAメチル化変化を惹起し、糖尿病性腎症の病態に関与する2019

    • Author(s)
      菱川彰人、林 香、中村真理、畔上達彦、吉本憲史、伊藤裕
    • Organizer
      抗加齢学会学術総会(最優秀演題賞受賞)
    • Related Report
      2019 Research-status Report
  • [Presentation] エピゲノム変化と慢性腎臓病病態との関連2019

    • Author(s)
      林 香、伊藤裕
    • Organizer
      抗加齢学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 尿中DNA修復因子KAT5/podocinの糖尿病患者における検討2019

    • Author(s)
      菱川彰人、林 香、中村真理、畔上達彦、吉本憲史、伊藤裕
    • Organizer
      抗加齢学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 糖尿病患者尿中脱落細胞におけるDNA修復因子KAT5, エピゲノム修飾因子の解析2019

    • Author(s)
      菱川彰人、林 香、中村真理、畔上達彦、吉本憲史、伊藤裕
    • Organizer
      日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腎ポドサイトにおけるKAT5発現低下はDNA 修復不全およびDNA メチル化変化を惹起する2019

    • Author(s)
      菱川彰人、林 香、畔上達彦、吉本憲史、伊藤裕
    • Organizer
      日本高血圧学会総会(YIA受賞)
    • Related Report
      2019 Research-status Report
  • [Presentation] 高血圧、糖尿病患者の尿中脱落細胞におけるDNA修復因子KAT5およびDNAメチル化修飾因子の解析2019

    • Author(s)
      菱川彰人、林 香、畔上達彦、吉本憲史、伊藤裕
    • Organizer
      日本高血圧学会総会(YIP受賞)
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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