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Elucidating the mechanisms of kidney fibrosis and regeneration

Research Project

Project/Area Number 26293202
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKyoto University

Principal Investigator

Yanagita Motoko  京都大学, 医学(系)研究科(研究院), 教授 (70378769)

Co-Investigator(Kenkyū-buntansha) 河本 宏  京都大学, 再生医科学研究所, 教授 (00343228)
Co-Investigator(Renkei-kenkyūsha) OKAMOTO Hitoshi  京都大学, 薬学研究科, 教授 (60158813)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords線維化 / 再生 / 炎症 / 老化 / 内科 / 再生医学 / 循環器 / 急性腎障害 / 慢性腎臓病 / 腎性貧血
Outline of Final Research Achievements

We demonstrated that proximal tubule injury induces the transdifferentiation of fibroblasts to myofibroblasts, and that the transdifferentiation is reversible when the proximal tubule injury is mild.
We also demonstrated that fibroblasts in aged kidney acquire the ability to produce homeostatic chemokines after injury, attract lymphocytes and trigger the formation of tertiary lymphoid tissues (TLTs). TLT formation in aged kidneys causes prolonged inflammation and delayed regeneration, and is frequently observed in aged human kidneys.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (34 results)

All 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 1 results,  Acknowledgement Compliant: 5 results) Presentation (22 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Remarks (2 results)

  • [Int'l Joint Research] University of San Diego/Regeneron Pharmaceuticals, Inc.(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of California, San Diego(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney2016

    • Author(s)
      Yuki Sato, Akiko Mii, Yoko Hamazaki, Harumi Fujita, Hirosuke Nakata, Kyoko Masuda, Shingo Nishiyama, Shinsuke Shibuya, Hironori Haga, Osamu Ogawa, Akira Shimizu, Shuh Narumiya, Tsuneyasu Kaisho, Makoto Arita, Masashi Yanagisawa, Masayuki Miyasaka, Kumar Sharma, Nagahiro Minato, Hiroshi Kawamoto, Motoko Yanagita
    • Journal Title

      JCI Insight

      Volume: 1(11)

    • NAID

      120005820865

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Insights into the Mechanisms of the Acute Kidney Injury-to-Chronic Kidney Disease Continuum2016

    • Author(s)
      Koji Takaori, Motoko Yanagita
    • Journal Title

      Nephron

      Volume: 134(3) Pages: 172-176

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Severity and frequency of proximal tubule injury determines renal prognosis2016

    • Author(s)
      Koji Takaori, Jin Nakamura, Shinya Yamamoto, Hirosuke Nakata, Yuki Sato, Masayuki Takase, Masaaki Nameta, Tadashi Yamamoto, Aris N. Economides, Kenji Kohno, Hironori Haga, Kumar Sharma, Motoko Yanagita
    • Journal Title

      J Am Soc Nephrol

      Volume: 27(8) Pages: 2393-406

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Time-dependent dysregulation of autophagy in the kidney: implications in aging and mitochondrial homeostasis2016

    • Author(s)
      Takeshi Yamamoto, Yoshitsugu Takabatake, Tomonori Kimura, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Jun-ya Kaimori, Isao Matsui, Harumi Kitamura, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka, Hiromi Rakugi
    • Journal Title

      Autophagy

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ENOS deficiency causes podocyte injury with mitochondrial abnormality2015

    • Author(s)
      Shuko Ueda, Shota Ozawa, Kiyoshi Mori, Katsuhiko Asanuma, Motoko Yanagita, Shunya Uchida, Takahiko Nakagawa
    • Journal Title

      Free Radical Biology & Medicine

      Volume: 87 Pages: 181-192

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-26a inhibits TGF-β-induced extracellular matrix expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy.2015

    • Author(s)
      Koga K, Yokoi H, Mori K, Kasahara K, Kuwabara T, Imamaki H, Ishii A, Mori KP, Kato Y, Ohno S, Toda N, Saleem MA, Sugawara A, Nakao K, Yanagita M, Mukoyama M.
    • Journal Title

      Diabetologia

      Volume: 58 Issue: 9 Pages: 2169-80

    • DOI

      10.1007/s00125-015-3642-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Exploring the origin and limitations of kidney regeneration.2015

    • Author(s)
      Endo T, Nakamura J, Sato Y, Asada M, Yamada R, Takase M, Takaori K, Oguchi A, Iguchi T, Higashi AY, Ohbayashi T, Nakamura T, Muso E, Kimura T, Yanagita M.
    • Journal Title

      J Pathol.

      Volume: 236(2) Issue: 2 Pages: 251-63

    • DOI

      10.1002/path.4514

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Origin of myofibroblasts and cellular events triggering fibrosis.2015

    • Author(s)
      Matthias Mack, Motoko Yanagita
    • Journal Title

      Kidney International

      Volume: 87 Issue: 2 Pages: 297-307

    • DOI

      10.1038/ki.2014.287

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] "Lessons from Animal Models of AKI to CKD Transition"2016

    • Author(s)
      Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Age-Dependent Tertiary Lymphoid Tissue Formation In The Kidney As A Novel Therapeutic Target"2016

    • Author(s)
      Yuki Sato, Akiko Mii, Hirosuke Nakata, Shingo Nishiyama, Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Lineage Tracing Analysis Elucidating the Behaviors of Erythropoietin Producing Cells"2016

    • Author(s)
      Keiichi Kaneko, Misako Asada, Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「老化と炎症」2016

    • Author(s)
      柳田 素子
    • Organizer
      第59回日本腎臓学会学術総会
    • Place of Presentation
      横浜、日本
    • Year and Date
      2016-06-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] 「ESRD治療の今後」2016

    • Author(s)
      柳田 素子
    • Organizer
      第61回日本透析医学会学術集会・総会
    • Place of Presentation
      大阪、日本
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Severity, Frequency and Prevalence of Proximal Tubule Injury Determines Renal Prognosis2015

    • Author(s)
      Koji Takaori, Jin Nakamura, Tadashi Yamamoto, Kumar Sharma, Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2015-11-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] Establishment of a Novel Mouse Strain to Trace Erythropoietin Producing Cells at Desired Time Points2015

    • Author(s)
      Keiichi Kaneko, Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego Convention Center
    • Year and Date
      2015-11-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肥満と腎障害2015

    • Author(s)
      柳田素子
    • Organizer
      第36回日本肥満学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] AKI to CKD Continuumにおける障害近位尿細管の役割2015

    • Author(s)
      高折光司、中村仁、山本伸也、柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05 – 2015-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] レチノイドシグナルを介した尿細管上皮・線維芽細胞相互作用の解明2015

    • Author(s)
      中村仁、小口綾貴子、山田龍、柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05 – 2015-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] AKIからCKD・末期腎不全への移行の分子基盤の解明2015

    • Author(s)
      柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05 – 2015-06-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] AKIからCKDへの移行の分子基盤の解明2015

    • Author(s)
      柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] AKI to CKD Continuumにおける障害近位尿細管の役割2015

    • Author(s)
      高折光司、中村仁、山本伸也、柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] レチノイドシグナルを介した尿細管上皮ー線維芽細胞相互作用の解明2015

    • Author(s)
      中村仁、小口綾貴子、柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] エリスロポエチン産生細胞の系譜追跡系の確立と線維化腎における動態の評価2015

    • Author(s)
      金子惠一、浅田三咲子、柳田素子
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腎臓病治療の将来:basic scienceからonconephrologyまで2015

    • Author(s)
      柳田素子
    • Organizer
      日本麻酔科学会 第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Selective proximal tubule injury causes interstitial fibrosis, distal tubule impairment and proteinuria2014

    • Author(s)
      Koji Takaori , Jin Nakamura, Tadashi Yamamoto, Motoko Yanagita
    • Organizer
      American Society of Nephrology Annual Meeting
    • Place of Presentation
      フィラデルフィア
    • Year and Date
      2014-11-11 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Exploring the pathophysiological functions of resident fibroblasts in the kidney2014

    • Author(s)
      Jin Nakamura, Akiko Oguchi, Ryo Yamada, Motoko Yanagita
    • Organizer
      American Society of Nephrology Annual Meeting
    • Place of Presentation
      フィラデルフィア
    • Year and Date
      2014-11-11 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cellular events and factors modulating fibrosis2014

    • Author(s)
      柳田素子
    • Organizer
      第57回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-04 – 2014-07-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 慢性腎臓病における上皮-線維芽細胞相互作用の解明2014

    • Author(s)
      中村 仁、小口 綾貴子、山田 龍、土田 潤一、柳田 素子
    • Organizer
      第57回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-04 – 2014-07-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 近位尿細管障害は線維化、遠位尿細管障害およびアルブミン尿を惹起する2014

    • Author(s)
      高折 光司、中村 仁、山本 格、柳田 素子
    • Organizer
      第57回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-04 – 2014-07-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腎臓病治療の可能性を探る:basic scienceからonco-nephrologyまで2014

    • Author(s)
      柳田素子
    • Organizer
      第59回日本透析医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2014-06-12 – 2014-06-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 京都大学医学研究科 腎臓内科学

    • URL

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

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学大学院医学研究科腎臓内科学

    • URL

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

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2022-06-09  

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