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Treating strategie for CKD with Klotho as a targetting molecule

Research Project

Project/Area Number 23591204
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionTokyo Women's Medical University

Principal Investigator

TSUCHIYA KEN  東京女子医科大学, 医学部, 准教授 (00246472)

Co-Investigator(Renkei-kenkyūsha) TSUCHIYA Mariko  東京女子医科大学, 医学部, 准教授 (00266826)
SHIOHIRA Shunji  東京女子医科大学, 医学部, 助教 (00529232)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsCKD / klotho / リン / 繊維化 / Klotho / 慢性腎臓病 / FGF23 / 線維化 / ESA / 生理活性 / 長寿命化 / トランスレーションリサーチ / マイクロアレイ / 老化
Research Abstract

Defects in Klotho gene expression in mice result in a syndrome resembling human aging that resembling with pathophysiology of chronic kidney disease (CKD). It has been clarified that membrane Klotho functions as a co-receptor for fibroblast growth factor 23 (FGF23) that regulate phosphate metabolism. Renal expression of the Klotho gene is markedly suppressed in CKD. Since renal fibrosis is a major risk factor for progression of CKD, renal interstitial fibrosis and Klotho expression should be correlated with each other. In this project, we explored the role and biological properties of Klotho, and especially focused on the phosphate metabolism, anti-fibrotic mechanism and clinical relevance of Klotho by measuring serum Klotho level in CKD. A reduction of Klotho expression aggravates renal interstitial fibrosis and that fibrosis-related factors regulate Klotho expression, making a vicious spiral in CKD. Thus, Klotho molecule is a targeting molecule in therapeutic strategy in CKD.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (20 results) (of which Invited: 1 results)

  • [Journal Article] Sphingosine-1-phosphate acts as a key molecule in the direct mediation of renal fibrosis.2013

    • Author(s)
      Shiohira S, Yoshida T, Sugiura H, Nishida M, Nitta K, Tsuchiya K.
    • Journal Title

      Physiological Reports

      Volume: - Issue: 7 Pages: e00172-e00172

    • DOI

      10.1002/phy2.172

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effects of the transcription factor Ets-1 on the expression of type I collagen in TGF-β1-stimulated renal epithelial cells.2012

    • Author(s)
      Okano K, Hibi A, Miyaoka T, Inoue T, Sugimoto H, Tsuchiya K, Akiba T, Nitta K.
    • Journal Title

      Mol Cell Biochem.

      Volume: 369 Issue: 1-2 Pages: 247-54

    • DOI

      10.1007/s11010-012-1388-6

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis.2012

    • Author(s)
      Sugiura H, Yoshida T, Shiohira S, Kohei J, Mitobe M, Kurosu H, Kuro-o M, Nitta K, Tsuchiya K.
    • Journal Title

      Am J Physiol Renal Physiol.

      Volume: 302 Issue: 10 Pages: F1252-F1264

    • DOI

      10.1152/ajprenal.00294.2011

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neutrophil gelatinase-associated lipocalin is a sensitive biomarker for the early diagnosis of acute rejection after living-donor kidney transplantation.2012

    • Author(s)
      Kohei J, Ishida H, Kazunari T, Tsuchiya K, Nitta K.
    • Journal Title

      Int Urol Nephrol.

      Volume: 0 Issue: 4 Pages: 1159-1167

    • DOI

      10.1007/s11255-012-0321-y

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolic syndrome and risk of progression of chronic kidney disease: a single-center cohort study in Japan.2012

    • Author(s)
      Saito T, Mochizuki T, Uchida K, Tsuchiya K, Nitta K.
    • Journal Title

      Heart Vessels.

      Volume: 0 Issue: 3 Pages: 323-329

    • DOI

      10.1007/s00380-012-0254-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Risk factors for vitamin D deficiency in patients with chronic kidney disease.2012

    • Author(s)
      Echida Y, Mochizuki T, Uchida K, Tsuchiya K, Nitta K.
    • Journal Title

      Intern Med.

      Volume: 51 Pages: 840-50

    • NAID

      130002061872

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced Klotho expression level in kidney ,,,2012

    • Author(s)
      Sugiura H, Yoshida T, Shiohira S, et al.
    • Journal Title

      Am J Physiol Renal Physiology 掲載確定

      Volume: XX

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] MafA is a key molecule in glucose and energy balance in the central nervous system and peripheral organs2011

    • Author(s)
      Tsuchiya M, Tsuchiya K, Yasuda K, Fujita K, Takinishi A, Furukawa M, Nitta K, Maeda A
    • Journal Title

      Int J Biomed Sci

      Volume: 7 Pages: 19-26

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614815/

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of klothos in the pathogenesis ,,,2011

    • Author(s)
      Sugiura H, Tsuchiya K, Nitta K.
    • Journal Title

      J Tokyo Wom Med Univ

      Volume: 81 Pages: 236-243

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] クロトー遺伝子2011

    • Author(s)
      土谷 健 杉浦秀和 新田孝作
    • Journal Title

      カレントテラピー

      Volume: 29 Pages: 119-119

    • Related Report
      2011 Research-status Report
  • [Presentation] Biological properties of klotho in the anti-fibrotic process and establishment of cell integrity in coordination with cell signaling pathway /translocation of membrane transporters2013

    • Author(s)
      Tsuchiya K, Shiohira S, Nishida M, Okano K, Sugiura H, Nitta K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2013-11-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Klotho is involved in the differentiation and establishment of cell integrity of pancreatic/adipose cell in coordination with transcriptional factor, mafs2013

    • Author(s)
      Tsuchiya M, Misaka R, Nitta K, Tsuchiya K
    • Organizer
      American Diabetes Association
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2013-06-21
    • Related Report
      2013 Final Research Report
  • [Presentation] siRNAとスクラッチアッセイによるSphingosine-1-phosphate receptor 3と腎臓線維化の解明2013

    • Author(s)
      潮平俊治、芳田工、公平順子、杉浦秀和、新田孝作、土谷健
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-10
    • Related Report
      2013 Final Research Report
  • [Presentation] Scratch assayを用いたKlothoの抗線維化作用の検討2013

    • Author(s)
      土谷健、杉浦秀和、潮平俊治、公平順子、鈴木美貴、望月俊雄、新田孝作
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-10
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 1) Klotho is involved in the differentiation and establishment of cell integrity of pancreatic/adipose cell in coordination with transcriptional factor, mafs2013

    • Author(s)
      Tsuchiya M, Misaka R, NItta K, and Tsuchiya K.
    • Organizer
      American Diabetes Association
    • Place of Presentation
      USA San Diego
    • Related Report
      2013 Annual Research Report
  • [Presentation] Biological Properties of Klotho in the Anti-Fibrotic Process and Establishment of Cell Integrity in Coordination with Cell Signaling Pathway /Translocation of Membrane Transporters2013

    • Author(s)
      Ken Tsuchiya, MD, PhD, Shunji Shiohira, MD, PhD, Miki Nishida, MD, Kazuhiro Okano, MD, PhD, Hidekazu Sugiura, MD, PhD, Kosaku Nitta, MD, PhD
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      USA Atlanta
    • Related Report
      2013 Annual Research Report
  • [Presentation] AKI CKD Klotho2013

    • Author(s)
      土谷 健
    • Organizer
      第24回急性血液浄化学会 教育セミナー
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Assessment of anti-fibrotic effects of klotho with a high-throughput cell migration assay using scratch wound healing2012

    • Author(s)
      Tsuchiya K, Sugiura H, Yosida T, Shiohira S, Nitta K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego USA
    • Year and Date
      2012-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3, potential mediators of renal fibrosis, are assessed by siRNA and scratch assay2012

    • Author(s)
      Shiohira S, Yoshida T, Kohei J, Sugiura H, Nitta K, Tsuchiya K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      San Diego USA
    • Year and Date
      2012-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Sphingosine-1-phosphateレセプター3は腎臓に繊維化に重要である2012

    • Author(s)
      潮平俊治、芳田工、公平順子、杉浦秀和、三戸部倫大、新田孝作、土谷健
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Klotho発現と腎線維化、TGF betaとの関連2012

    • Author(s)
      杉浦秀和、芳田工、公平順子、三戸部倫大、潮平俊治、土谷健、新田孝作
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 1) The WNT signaling pathway plays pivotal roles in the differentiation of pancreatic cells in coordination with maf transcriptional factors.2012

    • Author(s)
      Tsuchiya M, Tsuchiya K et al.
    • Organizer
      American Diabetes Association
    • Place of Presentation
      Philadelphia
    • Related Report
      2012 Research-status Report
  • [Presentation] 1) Assessment of anti-fibrotic effects of klotho with a high-throughput cell migration assay using scratch wound healing.2012

    • Author(s)
      Tsuchiya K, Sugiura H, Nitta K et al.
    • Organizer
      The American Society of Nephrology
    • Place of Presentation
      San Diego
    • Related Report
      2012 Research-status Report
  • [Presentation] 3) NGAL and cystatin C elevations were associated with short term graft function in overweight recipients after kidney transplantation.2012

    • Author(s)
      Kohei J, Tsuchiya K, Nitta K et al.
    • Organizer
      The American Society of Nephrology
    • Place of Presentation
      San Diego
    • Related Report
      2012 Research-status Report
  • [Presentation] Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis2011

    • Author(s)
      Sugiura H, Yoshida T, Kohei J, Shiohira S,Mitobe M, Tsuchiya K, Nitta K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Philadelphia USA
    • Year and Date
      2011-11-08
    • Related Report
      2013 Final Research Report
  • [Presentation] S1PR3 is pivotal factor in fibrosis in the kidney2011

    • Author(s)
      Shiohira S, Yoshida T, Kohei J,Sugiura H, Mitobe M, NittaK, Tsuchiya K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Philadelphia USA
    • Year and Date
      2011-11-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Klotho発現と腎線維化、TGF betaとの関連2011

    • Author(s)
      杉浦秀和、芳田工、三戸部倫大、潮平俊治、土谷健、新田孝作
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-06-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Sphingosine-1-phosphateは腎臓の線維化を直接的・間接的に促進する因子のひとつである2011

    • Author(s)
      潮平俊治、芳田工、公平順子、杉浦秀和、三戸部倫大、土谷健、新田孝作
    • Organizer
      日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-06-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Reduced Klotho Expression Level in Kidney ,,2011

    • Author(s)
      Sugiura H, Yoshida T, Shiohira S, et al
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      USA Philadelphia
    • Related Report
      2011 Research-status Report
  • [Presentation] Klotho発現と腎線維化、TGFとの関連

    • Author(s)
      杉浦 芳田 潮平
    • Organizer
      日本腎臓学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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