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Molecular mechanisms of mesangial matrix expansion in the progression of diabetic nephropathy

Research Project

Project/Area Number 25461221
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

Matsubara Takeshi  京都大学, 医学(系)研究科(研究院), 講師 (90422964)

Co-Investigator(Renkei-kenkyūsha) YANAGITA Motoko  京都大学, 大学院医学研究科・腎臓内科学, 教授 (70378769)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords病理学 / 糖尿病性腎症
Outline of Final Research Achievements

Diabetic nephropathy is pathologically characterized by the accumulation of extracellular matrix in the mesangium, of which the main component is α1/α2 type IV collagen (Col4). Recently, we identified Smad1 as a direct regulator of Col4 under diabetic conditions in vitro. Here, we demonstrate that Smad1 plays a key role in diabetic nephropathy through bone morphogenetic protein 4 (BMP4) in vivo. Smad1-overexpressing mice were established, and the induction of diabetes resulted in greater mesangial expansion. We also identified BMP4 as a regulatory factor of Smad1 in diabetic nephropathy and showed that diabetic mice treated with a BMP4-neutralizing antibody exhibited decreased Smad1 phosphorylation and less mesangial expansion than those with control IgG. Our data indicate that BMP4/Smad1 signaling is a critical cascade for the progression of mesangial expansion and that blocking this signal could be a novel therapeutic strategy for diabetic nephropathy.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in the Development of Diabetic Nephropathy.2015

    • Author(s)
      Matsubara T, Araki M, Abe H, Ueda O, Jishage K, Mima A, Goto C, Tominaga T, Kinosaki M, Kishi S, Nagai K, Iehara N, Fukushima N, Kita T, Arai H, Doi T.
    • Journal Title

      Diabetes

      Volume: 64 Issue: 8 Pages: 2978-2990

    • DOI

      10.2337/db14-0893

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease2015

    • Author(s)
      Nakagawa S, Nishihara K, Miyata H, Shinke H, Tomita E, Kajiwara M, Matsubara T, Iehara N, Igarashi Y, Yamada H, Fukatsu A, Yanagita M, Matsubara K & Masuda S
    • Journal Title

      PLoS One

      Volume: 10 Issue: 8 Pages: 1-14

    • DOI

      10.1371/journal.pone.0136994

    • NAID

      120005763422

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Onco-nephrology: current concepts and future perspectives2015

    • Author(s)
      Yuichiro Kitai, Takeshi Matsubara and Motoko Yanagita
    • Journal Title

      Jpn J Clin Oncol.

      Volume: 45 Issue: 7 Pages: 1-12

    • DOI

      10.1093/jjco/hyv035

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 【Onco-Nephrology-がん治療の最新フロンティア】 Onco-Nephrology なぜいま注目を集めているのか2015

    • Author(s)
      松原 雄, 比良野 圭太, 柳田 素子
    • Journal Title

      臨床泌尿器科

      Volume: 69 Pages: 534-539

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 【Onconephrology-腎臓病とがんの深いかかわり-】 腎不全患者のがん治療 腎不全患者におけるがん診療の実態2015

    • Author(s)
      松原 雄
    • Journal Title

      腎臓内科・泌尿器科

      Volume: 1 Pages: 61-67

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 腎不全患者におけるがん診療の実態2015

    • Author(s)
      松原 雄
    • Journal Title

      腎臓内科・泌尿器科

      Volume: 1 Pages: 61-67

    • Related Report
      2014 Research-status Report
  • [Journal Article] Onconephrology-なぜいま注目を集めているのか2015

    • Author(s)
      松原 雄, 比良野圭太, 柳田素子
    • Journal Title

      臨床泌尿器科

      Volume: 69 Pages: 1-8

    • Related Report
      2014 Research-status Report
  • [Journal Article] Physical finding of nutcracker phenomenon.2013

    • Author(s)
      Matsubara T, Ogawa O, Yanagita M.
    • Journal Title

      Kidney Int.

      Volume: 83(2) Issue: 2 Pages: 335-335

    • DOI

      10.1038/ki.2012.361

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical features and treatment of multicentric castleman's disease : a retrospective study of 21 Japanese patients at a single institute.

    • Author(s)
      Kawabata H, Kadowaki N, Nishikori M, Kitawaki T, Kondo T, Ishikawa T, Yoshifuji H, Yamakawa N, Imura Y, Mimori T, Matsumura Y, Miyachi Y, Matsubara T, Yanagita M, Haga H, Takaori-Kondo A.
    • Journal Title

      J Clin Exp Hematop.

      Volume: 53(1) Pages: 69-77

    • NAID

      10031183130

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 透析患者における抗がん剤治療の現状 慢性維持透析患者のがん診療実態調査 Onco-nephrology consortiumによる多施設共同観察研究2015

    • Author(s)
      松原 雄, 武藤 学, 福原 俊一, 柳田 素子
    • Organizer
      第60回日本透析医学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腎障害監視システム(Kidney Injury Surveillance System:KISS)の構築と外来発症腎障害患者における新たな危険因子の探索2015

    • Author(s)
      松原 雄, 西岡 敬祐, 遠藤 修一郎, 山田 博之, 宮田 仁美, 塚本 達雄, 柳田 素子
    • Organizer
      第60回日本透析医学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 外来発症腎障害の危険因子に関する検討2015

    • Author(s)
      松原 雄, 西岡 敬祐, 遠藤 修一郎, 山田 博之, 宮田 仁美, 塚本 達雄, 柳田 素子
    • Organizer
      第58回日本腎臓学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] Active Malignancy could be a Novel Risk Factor of Community-Acquired Acute Kidney Injury in Outpatients2015

    • Author(s)
      Takeshi Matsubara, Tatsuo Tsukamoto and Motoko Yanagita
    • Organizer
      C-KIN 2015, First Annual Conference
    • Place of Presentation
      Brussels
    • Year and Date
      2015-04-14 – 2015-04-15
    • Related Report
      2014 Research-status Report
  • [Presentation] 外来通院中の腎障害監視システムの構築と新たな腎障害危険因子の探索2015

    • Author(s)
      松原 雄, 西岡敬祐, 近藤尚哉, 遠藤修一郎, 山田博之, 宮田仁美, 塚本達雄, 柳田素子
    • Organizer
      第112回日本内科学会年次講演会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10 – 2015-04-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of Risk factors of Community-Acquired Acute Kidney Injury in Outpatients2014

    • Author(s)
      Takeshi Matsubara, Tatsuo Tsukamoto and Motoko Yanagita
    • Organizer
      ASN Kidney Week 2014
    • Place of Presentation
      Philadelphia
    • Year and Date
      2014-11-11 – 2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] 外来での急性腎障害を早期発見する試み2013

    • Author(s)
      松原 雄、荒木 真、牧野慎市、西岡敬祐、遠藤修一郎、宮田仁美、塚本達雄、柳田素子
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] 最新透析医療2015

    • Author(s)
      松原 雄、武藤 学、柳田素子
    • Total Pages
      859
    • Publisher
      医歯薬ジャーナル社
    • Related Report
      2015 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
      2015 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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