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Investigation of a novel therapy for renal diseases by inhibiting CTGF

Research Project

Project/Area Number 23591190
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YOKOI HIDEKI  京都大学, 医学(系)研究科(研究院), 特定病院助教 (90378779)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords内科 / 腎臓内科 / 糸球体腎炎 / 糸球体 / 腎炎 / マクロファージ / 線維化 / 腎不全 / 炎症 / 糖尿病性腎症 / 抗糸球体基底膜抗体腎炎 / ノックアウトマウス / floxedマウス / タモキシフェン
Research Abstract

Connective tissue growth factor (CTGF/CCN2) regulates signaling of other growth factors and promotes fibrosis. We examined the role of CTGF in diabetic nephropathy and in anti-glomerular basement membrane (anti-GBM) nephritis, using conditional CTGF knockout mice. Systemic inducible CTGF knockout (ROSA-CTGF cKO) mice and podocyte-specific CTGF knockout mice exhibited no apparent phenotypic changes in streptozotocin-induced diabetic nephropathy. In anti-GBM nephritis model, ROSA-CTGF cKO mice ameliorated proteinuria by 50%, macrophage infiltration in glomeruli by 40%, glomerular changes including crescentic formation, extracellular matrix deposition and thickness of GBM in electron microscopic analysis compared with control mice.

Report

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

    (19 results)

All 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (8 results) Remarks (3 results)

  • [Journal Article] Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases2014

    • Author(s)
      Kuwabara T, Mori K, Kasahara M, Yokoi H, Imamaki H, Ishii A, Koga K, Sugawara A, Yasuno S, Ueshima K, Morikawa T, Konishi Y, Imanishi M, Nishiyama A, Nakao K, Mukoyama M
    • Journal Title

      PloS One

      Volume: 9 Issue: 2 Pages: e88942-e88942

    • DOI

      10.1371/journal.pone.0088942

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Do statins play a role in renoprotection?2014

    • Author(s)
      Kasahara M, Nakagawa T, Yokoi H, Kuwabara T, Yasuno S, Mori K, Mukoyama M
    • Journal Title

      Ueshima K. Clin Exp Nephrol

      Volume: 18 Issue: 2 Pages: 282-285

    • DOI

      10.1007/s10157-013-0928-z

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Do statins play a role in renoprotection?2014

    • Author(s)
      Kasahara M, Nakagawa T, Yokoi H, Kuwabara T, Yasuno S, Mori K, Mukoyama M, Ueshima K.
    • Journal Title

      Clin Exp Nephrol

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3,4-dideoxyglucosone-3-ene in mice2013

    • Author(s)
      Yokoi, H., Kasahara, M., Mori, K., Kuwabara, T., Toda, N., Yamada, R., Namoto, S., Yamamoto, T., Seki, N., Souma, N., Yamaguchi, T., Sugawara, A., Mukoyama, M., Nakao, K.
    • Journal Title

      Peritoneal Dialysis International

      Volume: 33(2) Issue: 2 Pages: 143-154

    • DOI

      10.3747/pdi.2011.00033

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury2012

    • Author(s)
      Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Kato Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Tokudome T, Kishimoto I, Sugawara A, Nakao K
    • Journal Title

      J Am Soc Nephrol

      Volume: 23:1198-1209 Issue: 7 Pages: 1198-1209

    • DOI

      10.1681/asn.2011100985

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice2012

    • Author(s)
      Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Ogawa Y, Imamaki H, Kawanishi T, Ishii A, Koga K, Mori KP, Kato Y, Sugawara A, Nakao K
    • Journal Title

      Diabetologia

      Volume: 55:2256-2266 Issue: 8 Pages: 2256-2266

    • DOI

      10.1007/s00125-012-2578-1

    • NAID

      120004225542

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis2012

    • Author(s)
      Yokoi H, Nakao K, et al
    • Journal Title

      Kidney Int.

      Volume: 81 Issue: 2 Pages: 160-169

    • DOI

      10.1038/ki.2011.305

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by toll-like receptor 4 in mice2012

    • Author(s)
      Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Imamaki H, Kawanishi T, Ishii A, Koga K, Mori PK, Kato Y, Nakao K.
    • Journal Title

      Diabetologia

      Volume: in press

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Systemic Deletion of CTGF Ameliorates Anti-Glomerular Basement Membrane Nephritis with Reduction of Macrophage Infiltration2013

    • Author(s)
      N.Toda, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, T.Matsusaka, K.Nakao, M.Mukoyama
    • Organizer
      米国腎臓病学会年次総会
    • Place of Presentation
      米国アトランタ
    • Related Report
      2013 Final Research Report
  • [Presentation] 中尾一和抗糸球体基底膜(GBM)腎炎におけるCTGFの意義2013

    • Author(s)
      戸田尚宏、横井秀基、笠原正登、森潔、桒原孝成、今牧博貴、石井輝、古賀健一、森慶太、加藤有希子、大野祥子、菅原照、向山政志
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗糸球体基底膜(GBM)腎炎におけるCTGFの意義2013

    • Author(s)
      戸田尚宏、横井秀基、笠原正登、森 潔、桒原孝成、今牧博貴、石井輝、古賀健一、森慶太、加藤有希子、大野祥子、菅原照、向山政志、中尾一和
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Systemic Deletion of CTGF Ameliorates Anti-Glomerular Basement Membrane Nephritis with Reduction of Macrophage Infiltration2013

    • Author(s)
      N.Toda, H.yokoi, M,Kasahara, K,Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, T.Matsusaka, K.Nakao, M.Mukoyama
    • Organizer
      Annual Meeting of American Society of Nephrology
    • Place of Presentation
      Atlanta, GA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Inducible CTGF (CCN2) Knockout Mice Attenuates Anti-Glomerular Basement Membrane Nephritis2012

    • Author(s)
      ③N.Toda, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, M.Mukoyama, K.Nakao 2012年10月30日-11月4日
    • Organizer
      米国腎臓病学会年次総会
    • Place of Presentation
      サンディエゴ、米国
    • Related Report
      2013 Final Research Report
  • [Presentation] Inducible CTGF (CCN2) Knockout Mice Attenuates Anti-Glomerular Basement Membrane Nephritis2012

    • Author(s)
      N.Toda, H.Yokoi, M.Kasahara, K.Mori, T.Kuwabara, H.Imamaki, K.Koga, A.Ishii, Y.Kato, K.P.Mori, S.Ohno, A.Sugawara, M.Mukoyama, K.Nakao
    • Organizer
      American Society of Nephrology Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional analysis of miR-30c, miR-26a and miR-379 in podocytes and their potential roles in diabetic nephropathy2011

    • Author(s)
      K.Koga, H.Yokoi, M.Mukoyama, K.Mori, M.Kasahara, T.Kuwabara, H.Imamaki, T.kawanishi, A.Ishii, K.P.Mori, Y.Kato, M.Saleem, A.Sugawara, K.Nakao
    • Organizer
      米国腎臓病学会年次総会
    • Place of Presentation
      フィラデルフィア、米国
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional analysis of miR-30c, miR-26a and miR-379 in podocytes and their potential roles in diabetic nephropathy2011

    • Author(s)
      Koga K, Yokoi H, Mukoyama M, Mori K, Kasahara M, Kuwabara T, Imamaki H, Kawanishi T, Ishii A, Mori PK, Kato Y, Saleem M, Sugawara A, Nakao K
    • Organizer
      American Society of Nephrology
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2011 Research-status Report
  • [Remarks] 京都大学腎臓内科ホームページ

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 京都大学大学院医学研究科内科学講座 内分泌代謝内科

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html

    • Related Report
      2012 Research-status Report
  • [Remarks] webページ

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html

    • Related Report
      2011 Research-status Report

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

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