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2022 Fiscal Year Annual Research Report

Spiral progression of DNA damage repair, epigenetic alterations and metabolic changes in metabolic kidney diseases

Research Project

Project/Area Number 20H00535
Research InstitutionKeio University

Principal Investigator

伊藤 裕  慶應義塾大学, 医学部(信濃町), 教授 (40252457)

Co-Investigator(Kenkyū-buntansha) 林 香  慶應義塾大学, 医学部(信濃町), 講師 (60445294)
神田 武志  慶應義塾大学, 医学部(信濃町), 講師 (80317114)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywordsニコチン酸代謝 / DNA損傷 / エピゲノム
Outline of Annual Research Achievements

申請者は、ニコチン酸アミドジヌクレオチド(NAD) 代謝の中間代謝産物であるニコチンアミドモノヌクレオチド(NMN)の近位尿細管における産生低下が糖尿病性腎臓病(Diabetic kidney disease, DKD)の病態に関与していることを報告しているが、更に最近DKDモデル
マウスへのNMN投与により尿アルブミンの改善が認められることを報告した(Yasuda, et al. JASN 2021)。この成果に基づき2022年度は更にヒトへの臨床応用を目指した投与
経路や量の検討をサルを用いて行った。今後、NMN投与によるDNA損傷修復に対する効果について更に検討する予定である。
一方、腎臓構成細胞におけるDNA損傷修復による代謝変容への影響に関しては、腎臓細胞(ポドサイト、近位尿細管細胞)特異的にDNA損傷を惹起する遺伝子改変マウスを用いた検討を行った。ポドサイトにおけるDNA損傷の反復は、ネフローゼ症候群、腎不全を来したが、ポドサイト遺伝子のDNAメチル化亢進、形質変化のみならず、末梢血のDNAメチル化変化、メモリーT細胞分画の増加をもたらすことが明らかになった(Nakamichi, et al. Cell Rep 2023)。一方、近位尿細管上皮細胞におけるDNA損傷修復は、全身の代謝変容をもたらすことが示唆されており、代謝臓器間シグナルを結びつける因子について、シングルセルRNA-seq解析、DNAメチル化解析の手法を用いて検討を進めている。

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

  • Research Products

    (16 results)

All 2023 2022

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 9 results)

  • [Journal Article] Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats2023

    • Author(s)
      Matsui Ayumi、Yoshifuji Ayumi、Irie Junichiro、Tajima Takaya、Uchiyama Kiyotaka、Itoh Tomoaki、Wakino Shu、Itoh Hiroshi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 27 Pages: 295~308

    • DOI

      10.1007/s10157-022-02312-y

    • Peer Reviewed
  • [Journal Article] Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria2023

    • Author(s)
      Yoshimoto Norifumi、Hayashi Kaori、Hishikawa Akihito、Hashiguchi Akinori、Nakamichi Ran、Sugita-Nishimura Erina、Yoshida-Hama Eriko、Azegami Tatsuhiko、Nakayama Takashin、Itoh Hiroshi
    • Journal Title

      Hypertension Research

      Volume: 46 Pages: 1000~1008

    • DOI

      10.1038/s41440-023-01169-2

    • Peer Reviewed / Open Access
  • [Journal Article] NAD+ and mtRNA sensing drive human kidney diseases2023

    • Author(s)
      Itoh Hiroshi、Yoshino Jun
    • Journal Title

      Nature Metabolism

      Volume: 5 Pages: 357~359

    • DOI

      10.1038/s42255-023-00762-6

    • Peer Reviewed
  • [Journal Article] “Endocrine Supremacism” of new version in the Anthropocene2023

    • Author(s)
      Itoh Hiroshi
    • Journal Title

      Endocrine Journal

      Volume: 70 Pages: 233~240

    • DOI

      10.1507/endocrj.EJ20221130

    • Peer Reviewed
  • [Journal Article] DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation2023

    • Author(s)
      Nakamichi Ran、Hishikawa Akihito、Chikuma Shunsuke、Yoshimura Akihiko、Sasaki Takashi、Hashiguchi Akinori、Abe Takaya、Tokuhara Tomoko、Yoshimoto Norifumi、Nishimura Erina Sugita、Hama Eriko Yoshida、Azegami Tatsuhiko、Nakayama Takashin、Hayashi Kaori、Itoh Hiroshi
    • Journal Title

      Cell Reports

      Volume: 42 Pages: 112427~112427

    • DOI

      10.1016/j.celrep.2023.112427

    • Peer Reviewed / Open Access
  • [Journal Article] Correction: Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification2023

    • Author(s)
      Jo Rie、Shibata Hirotaka、Kurihara Isao、Yokota Kenichi、Kobayashi Sakiko、Murai-Takeda Ayano、Mitsuishi Yuko、Hayashi Takeshi、Nakamura Toshifumi、Itoh Hiroshi
    • Journal Title

      Hypertension Research

      Volume: 46 Pages: 814~814

    • DOI

      10.1038/s41440-023-01167-4

    • Peer Reviewed / Open Access
  • [Journal Article] Sodium benzoate attenuates 2,8-dihydroxyadenine nephropathy by inhibiting monocyte/macrophage TNF-α expression2023

    • Author(s)
      Oshima Yoichi、Wakino Shu、Kanda Takeshi、Tajima Takaya、Itoh Tomoaki、Uchiyama Kiyotaka、Yoshimoto Keiko、Sasabe Jumpei、Yasui Masato、Itoh Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 13 Pages: -

    • DOI

      10.1038/s41598-023-30056-6

    • Peer Reviewed / Open Access
  • [Journal Article] Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection2023

    • Author(s)
      Nakayama Takashin、Azegami Tatsuhiko、Kiso Maki、Imai Masaki、Uraki Ryuta、Hayashi Kaori、Hishikawa Akihito、Yoshimoto Norifumi、Nakamichi Ran、Sugita-Nishimura Erina、Yoshida-Hama Eriko、Kawaoka Yoshihiro、Itoh Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 13 Pages: -

    • DOI

      10.1038/s41598-023-30305-8

    • Peer Reviewed / Open Access
  • [Journal Article] Activation of the intestinal tissue renin-angiotensin system by transient sodium loading in salt-sensitive rats2022

    • Author(s)
      Ryuzaki Masaki、Miyashita Kazutoshi、Sato Masaaki、Inoue Hiroyuki、Fujii Kentaro、Hagiwara Aika、Uto Asuka、Endo Sho、Oshida Takuma、Kinouchi Kenichiro、Itoh Hiroshi
    • Journal Title

      Journal of Hypertension

      Volume: 40 Pages: 33~45

    • DOI

      10.1097/HJH.0000000000002974

    • Peer Reviewed
  • [Journal Article] The significance of NAD+metabolites and nicotinamide N-methyltransferase in chronic kidney disease2022

    • Author(s)
      Takahashi Rina、Kanda Takeshi、Komatsu Motoaki、Itoh Tomoaki、Minakuchi Hitoshi、Urai Hidenori、Kuroita Tomohiro、Shigaki Shuhei、Tsukamoto Tasuku、Higuchi Naoko、Ikeda Minoru、Yamanaka Risa、Yoshimura Norito、Ono Takashi、Yukioka Hideo、Hasegawa Kazuhiro、Tokuyama Hirobumi、Wakino Shu、Itoh Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 12 Pages: -

    • DOI

      10.1038/s41598-022-10476-6

    • Peer Reviewed / Open Access
  • [Journal Article] Intestinal Epithelial NAD+ Biosynthesis Regulates GLP-1 Production and Postprandial Glucose Metabolism in Mice2022

    • Author(s)
      Nagahisa Taichi、Yamaguchi Shintaro、Kosugi Shotaro、Homma Koichiro、Miyashita Kazutoshi、Irie Junichiro、Yoshino Jun、Itoh Hiroshi
    • Journal Title

      Endocrinology

      Volume: 163 Pages: -

    • DOI

      10.1210/endocr/bqac023

    • Peer Reviewed
  • [Journal Article] Home-Based Exercise Program Ameliorates Renal Function Decline in Patients With CKD Stage 42022

    • Author(s)
      Adachi Keika、Uchiyama Kiyotaka、Muraoka Kaori、Nakayama Takashin、Yasuda Marie、Miyashita Kazutoshi、Tokuyama Hirobumi、Wakino Shu、Itoh Hiroshi
    • Journal Title

      Kidney International Reports

      Volume: 7 Pages: 899~903

    • DOI

      10.1016/j.ekir.2022.01.006

    • Peer Reviewed / Open Access
  • [Journal Article] Lysine-specific demethylase 1 as a corepressor of mineralocorticoid receptor2022

    • Author(s)
      Kohata Nao、Kurihara Isao、Yokota Kenichi、Kobayashi Sakiko、Murai-Takeda Ayano、Mitsuishi Yuko、Nakamura Toshifumi、Morisaki Mitsuha、Kozuma Takahide、Torimitsu Takuto、Kawai Miki、Itoh Hiroshi
    • Journal Title

      Hypertension Research

      Volume: 45 Pages: 641~649

    • DOI

      10.1038/s41440-022-00859-7

    • Peer Reviewed / Open Access
  • [Journal Article] Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy2022

    • Author(s)
      Yasuda Itaru、Hasegawa Kazuhiro、Sakamaki Yusuke、Muraoka Hirokazu、Kawaguchi Takahisa、Kusahana Ei、Ono Takashi、Kanda Takeshi、Tokuyama Hirobumi、Wakino Shu、Itoh Hiroshi
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 32 Pages: 1355~1370

    • DOI

      10.1681/ASN.2020081188

    • Peer Reviewed
  • [Journal Article] Vaccination against connective tissue growth factor attenuates the development of renal fibrosis2022

    • Author(s)
      Nakayama Takashin、Azegami Tatsuhiko、Hayashi Kaori、Hishikawa Akihito、Yoshimoto Norifumi、Nakamichi Ran、Sugita Erina、Itoh Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 12 Pages: -

    • DOI

      10.1038/s41598-022-15118-5

    • Peer Reviewed / Open Access
  • [Journal Article] Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage2022

    • Author(s)
      Ida-Naitoh Makiko、Tokuyama Hirobumi、Futatsugi Koji、Yasuda Marie、Adachi Keika、Kanda Takeshi、Tanabe Yoshiyuki、Wakino Shu、Itoh Hiroshi
    • Journal Title

      Kidney International

      Volume: 102 Pages: 798~814

    • DOI

      10.1016/j.kint.2022.05.018

    • Peer Reviewed

URL: 

Published: 2023-12-25  

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