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腎臓の修復を担う幹細胞とそのニッチ環境の加齢に伴う変容の解明

Publicly Offered Research

Project AreaEstablishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging
Project/Area Number 17H05642
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

柳田 素子  京都大学, 医学研究科, 教授 (70378769)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords修復 / 幹細胞
Outline of Annual Research Achievements

高齢者は急激に腎機能が低下する急性腎障害(Acute Kidney Injury: AKI)に罹患しやすく、しかも回復しにくい(Ishani A et al. J Am Soc Nephrol 2009)が、老化した腎臓の障害応答性低下のメカニズムには不明な点が多い。腎臓の機能単位ネフロンは、血液を濾過する糸球体と、糸球体で濾過された原尿から溶質を取捨選択する尿細管から成り立っている。急性腎障害では主として近位尿細管が障害されるが、若齢個体では障害後に著明な細胞増殖が起こり、元通りに修復されるのに対して、高齢個体では修復力が低下している。近位尿細管の修復を担う細胞の由来については諸説あり、議論は混迷を極めていた。申請者らは独自の遺伝子組み換え動物を用いた近位尿細管の系譜追跡実験を行い、生き残った近位尿細管に含まれる細胞が修復を担うこと、障害が強いと修復が不完全であること(Yanagita M et al. J Pathol 2015)を証明したが、近位尿細管細胞に幹・前駆細胞が存在するのか、全ての近位尿細管細胞が修復を担うのかは明らかではなかった。
申請者は特定の転写因子がごく少数の近位尿細管に発現することに注目し、その細胞の系譜追跡実験を行ったところ、近位尿細管にごく少数の標識細胞が存在し、腎障害後に急激に増加することを見出した(未発表)。申請者は同標識細胞の局在や数、同細胞除去時の腎修復の変化、同標識細胞と他の近位尿細管の遺伝子発現プロファイルを比較した。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (12 results)

All 2019 2018 2017 Other

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] Myofibroblasts acquire retinoic acid?producing ability during fibroblast-to-myofibroblast transition?following kidney injury2019

    • Author(s)
      Nakamura Jin、Sato Yuki、Kitai Yuichiro、Wajima Shuichi、Yamamoto Shinya、Oguchi Akiko、Yamada Ryo、Kaneko Keiichi、Kondo Makiko、Uchino Eiichiro、Tsuchida Junichi、Hirano Keita、Sharma Kumar、Kohno Kenji、Yanagita Motoko
    • Journal Title

      Kidney International

      Volume: 95 Issue: 3 Pages: 526-539

    • DOI

      10.1016/j.kint.2018.10.017

    • NAID

      120006550402

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immune cells and inflammation in AKI to CKD progression2018

    • Author(s)
      Sato Yuki、Yanagita Motoko
    • Journal Title

      American Journal of Physiology-Renal Physiology

      Volume: 315 Issue: 6 Pages: F1501-F1512

    • DOI

      10.1152/ajprenal.00195.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis2018

    • Author(s)
      Asao Rin、Seki Takuto、Takagi Miyuki、Yamada Hiroyuki、Kodama Fumiko、Hosoe-Nagai Yoshiko、Tanaka Eriko、Trejo Juan Alejandro Oliva、Yamamoto-Nonaka Kanae、Sasaki Yu、Hidaka Teruo、Ueno Takashi、Yanagita Motoko、Suzuki Yusuke、Tomino Yasuhiko、Asanuma Katsuhiko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 5061-5061

    • DOI

      10.1038/s41598-018-23278-6

    • NAID

      120006517798

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease.2018

    • Author(s)
      Iguchi T, Takaori K, Mii A, Sato Y, Suzuki Y, Yoshifuji H, Seno H, Ogawa O, Omori K, Bessho K, Kondo S, Yoshizaki T, Nakashima H, Saito T, Mimori T, Haga H, Kawano M, Yanagita M.
    • Journal Title

      Mod Pathol.

      Volume: - Issue: 6 Pages: 890-899

    • DOI

      10.1038/s41379-018-0036-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] “Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related disease”2018

    • Author(s)
      Iguchi T, Takaori K, Mii A, Sato Y, Suzuki Y, Yoshifuji H, Seno H, Ogawa O, Omori K, Bessho K, Kondo S, Yoshizaki T, Nakashima H, Saito T, Mimori T , Haga H, Kawano M,Yanagita M.
    • Journal Title

      Mod Pathol.

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resident fibroblasts in the kidney: a major driver of fibrosis and inflammation.2017

    • Author(s)
      Yuki Sato, Motoko Yanagita
    • Journal Title

      Inflammation and regeneration

      Volume: 37 Issue: 1

    • DOI

      10.1186/s41232-017-0048-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 近位尿細管細胞と線維芽細胞のクロストーク:障害、修復と線維化2018

    • Author(s)
      柳田素子
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regeneration of proximal tubules after severe injury depends on clonal proliferation of eR1-activated subpopulation of proximal tubular cells2018

    • Author(s)
      Yuichiro Kitai, Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日常診療における難治性疾患への対応とピットフォール2018

    • Author(s)
      柳田素子
    • Organizer
      第115回日本内科学会講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Epithelial Pericyte Reciprocal Signaling in AKI:Basic/Clinical Science Session2017

    • Author(s)
      Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] シンポジウム:老化腎の可塑性低下のメカニズム2017

    • Author(s)
      柳田素子
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Remarks] 京都大学腎臓内科学

    • URL

      http://www.kidney.kuhp.kyoto-u.ac.jp

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2019-12-27  

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