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MOLECULAR MECHANISM OF GLOMERULOSCLEROSIS IN AGING

Research Project

Project/Area Number 21790808
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionKyoto University

Principal Investigator

MATSUBARA Takeshi  京都大学, 医学研究科, 助教 (90422964)

Co-Investigator(Renkei-kenkyūsha) ARAI Hidenori  京都大学, 医学研究科, 教授 (60232021)
ABE Hideharu  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60399342)
DOI Toshio  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60183498)
IEHARA Noriyuki  京都大学, 医学研究科, 助教 (20281727)
Research Collaborator NAGAI Kojiro  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教
MIMA Akira  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教
Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords老化 / 細胞・組織 / 病理学
Research Abstract

Glomerulosclerosis is the most common cause of chronic renal failure in aging. It is pathologically characterized by the accumulation of extracellular matrix in mesangium, of which main component is type IV collagen (Col4). Recently, we identified Smad1 as a direct regulator of Col4 under diabetic condition in vitro. To elucidate the mechanism of glomerulosclerosis in aging, we addressed the role of Smad1 in glomerulosclerosis during diabetes. First, we showed overexpression of Smad1 exacerbates glomerulosclerosis in diabetic mice, and identified bone morphogenetic protein 4 (BMP4) as a potent stimulator of Smad1 during diabetes. Now we are checking the role of BMP4 for biological aging process. Id (Inhibitor of differentiation), one of the important transcriptional factors regulated by Smad1, is known to inhibit basic-helix loop helix protein such as E2A, and to regulate cellular senescence. We showed that PIASy, which was also identified as a regulator of cellular senescence, is also a novel E2A binding partner, and enhances its sumoylation as a specific SUMO-E3 ligase, leading to down-regulate phenotypic changes of mesangial cells.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (23 results)

All 2011 2010 2009

All Journal Article (9 results) (of which Peer Reviewed: 8 results) Presentation (14 results)

  • [Journal Article] Sox9 induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy2011

    • Author(s)
      Kishi S, Abe H, Akiyama H, Tominaga T, Murakami T, Mima A, Nagai K, Kishi F, Matsuura M, Matsubara T, Iehara N, Ueda O, Fukushima N, Jishage KI, Doi T.
    • Journal Title

      J Biol Chem

      Volume: 286(37) Issue: 37 Pages: 32162-9

    • DOI

      10.1074/jbc.m111.244541

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy2011

    • Author(s)
      Tominaga T, Abe H, Ueda O, Goto C, Nakahara K, Murakami T, Mima A, Nagai K, Araoka T, Kishi S, Fukushima N, Jishage KI, Doi T
    • Journal Title

      J Biol Chem

      Volume: 286(22) Issue: 22 Pages: 20109-16

    • DOI

      10.1074/jbc.m110.179382

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of Src mediates PDGF-induced Smad1 phosphorylation and contributes to the progression of glomerulosclerosis in glomerulonephritis2011

    • Author(s)
      Mima A, Abe H, Nagai K, Arai H, Matsubara T, Araki M, Torikoshi K, Tominaga T, Iehara N, Fukatsu A, Kita T, Doi T
    • Journal Title

      PLoS One.

      Volume: 6(3) Issue: 3 Pages: e17929-e17929

    • DOI

      10.1371/journal.pone.0017929

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Smad1 in diabetic nephropathy: Molecular mechanisms and implications as a diagnostic marker2011

    • Author(s)
      Abe H, Matsubara T, Arai H, Doi T
    • Journal Title

      Histol Histopathol.

      Volume: 26(4) Pages: 531-41

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 電解質異常 (低カリウム血症, 高カルシウム血症) (特集 腎障害をきたす全身性疾患--最近の進歩)2011

    • Author(s)
      松原雄, 家原典之, 深津敦司
    • Journal Title

      日本内科学会雑誌

      Volume: 100(5) Pages: 1313-1318

    • Related Report
      2010 Final Research Report
  • [Journal Article] SOX9 protein induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy2011

    • Author(s)
      Kishi S, 著者8名省略, Matsubara T, 著者4名省略, Doi T
    • Journal Title

      J Biol Chem

      Volume: 286(37) Pages: 32162-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy2011

    • Author(s)
      Tominaga T, 著者5名省略, Matsubara T, 著者6名省略, Doi T
    • Journal Title

      J Biol Chem

      Volume: 286(22) Pages: 20109-16

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of Src mediates PDGF-induced Smad1 phosphorylation and contributes to the progression of glomerulosclerosis in glomerulonephritis2011

    • Author(s)
      Mima A, 著者3名省略, Matsubara T, 著者6名省略, Doi T
    • Journal Title

      PLoS One

      Volume: 6(3)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcription factor 7-like 2(TCF7L2) regulates activin receptor-like kinase 1(ALK1)/ Smad1 pathway for development of diabetic nephropathy2010

    • Author(s)
      Araoka T, Abe H, Tominaga T, Mima A, Matsubara T, Murakami T, Kishi S, Nagai K, Doi T
    • Journal Title

      Mol Cells

      Volume: 30(3) Issue: 3 Pages: 209-218

    • DOI

      10.1007/s10059-010-0109-9

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 低ナトリウム血症とその治療2011

    • Author(s)
      松原雄, 家原典之, 土井俊夫
    • Organizer
      第41回日本腎臓学会西部学術大会
    • Place of Presentation
      徳島
    • Year and Date
      2011-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] IV型コラーゲンα5鎖の新規変異と濃厚な家族歴を有し、遺伝性腎炎が疑われた一例2011

    • Author(s)
      松原雄, 長尾和浩, 他
    • Organizer
      第41回日本腎臓学会西部学術大会
    • Place of Presentation
      徳島
    • Year and Date
      2011-09-30
    • Related Report
      2010 Final Research Report
  • [Presentation] OVEREXPRESSION OF Smad1 EXACERBATES GLOMERULAR LESIONS IN DIABETIC NEPHROPATHY THROUGH BMP-42011

    • Author(s)
      Takeshi Matsubara, Hideharu Abe, et. al
    • Organizer
      The World Congress of Nephrology 2011
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2011-08-04
    • Related Report
      2010 Final Research Report
  • [Presentation] BMP4/Smad1 Signaling: A Novel Therapeutic Target for the Progression of Diabetic Nephropathy, (Oral presentation)2011

    • Author(s)
      Takeshi Matsubara, Hideharu Abe, et. Al
    • Organizer
      the American Diabetes Association's 71st Scientific Sessions
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2011-06-26
    • Related Report
      2010 Final Research Report
  • [Presentation] BMP4/Smad1 Signaling : A Novel Therapeutic Target for the Progression of Diabetic Nephropathy2011

    • Author(s)
      Takeshi Matsubara, 他
    • Organizer
      the American Diabetes Association's 71st Sdentific Sessions
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2011-06-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 糖尿病性腎症における糸球体硬化とアルブミン尿には異なる病態形成機構が存在する2011

    • Author(s)
      松原雄, 安部秀斉, 他
    • Organizer
      第54回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-06-17
    • Related Report
      2010 Final Research Report
  • [Presentation] PIASyはメサンギウム細胞においてE12と共役し<SMAの発現を制御する2011

    • Author(s)
      鳥越和雄, 大島隆幸, 平野隆弘, 安部秀斉, 松雄, 荒木真, 家原典之, 深津敦司, 荒井秀典, 土井俊夫
    • Organizer
      第54回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-06-17
    • Related Report
      2010 Final Research Report
  • [Presentation] BMP4/Smad1 Signaling Is a Critical Therapeutic Target for Diabetic Nephropathy2010

    • Author(s)
      Takeshi Matsubara, Hideharu Abe, et. al
    • Organizer
      Renal Week 2010 American Society of Nephrology Annual Meeting
    • Place of Presentation
      Denver, CO, USA
    • Year and Date
      2010-11-17
    • Related Report
      2010 Final Research Report
  • [Presentation] IV型コラーゲンの転写制御因子Smad1は骨形成因子BMP4を介して糖尿病性腎症進展に中心的役割を果たす2010

    • Author(s)
      松原雄, 安部秀斉, 他
    • Organizer
      糖尿病合併症学会
    • Place of Presentation
      大津
    • Year and Date
      2010-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 経時的に観察し得た移植後膜性腎症の一例2010

    • Author(s)
      松原雄, 大久保和俊, 他
    • Organizer
      第40回日本腎臓学会西部学術大会
    • Place of Presentation
      広島
    • Year and Date
      2010-10-08
    • Related Report
      2010 Final Research Report
  • [Presentation] Overexpression of Smad1 Causes Remarkable Glomerulosclerosis in Diabetic Mice2010

    • Author(s)
      Takeshi Matsubara, Hideharu Abe, Otoya Ueda, Kou-ichi Jishage, Akira Mima, Chisato Goto, Tatsuya Tominaga, Makoto Araki, Kazuo Torikoshi, Kojiro Nagai, Noriyuki Iehara, Atsushi Fukatsu, Naoshi Fukushima, Hidenori Arai, Toshio Doi
    • Organizer
      the American Diabetes Association's 70th Scientific Sessions
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2010-06-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 糖尿病性腎症に関わる新たな治療標的分子の検討2010

    • Author(s)
      松原雄, 安部秀斉, 他
    • Organizer
      第53回日本腎臓学会学術総会
    • Place of Presentation
      神戸
    • Year and Date
      2010-06-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Smad1は糖尿病性糸球体硬化症の進展に重要な役割を果たす2010

    • Author(s)
      松原雄, 安部秀斉, 他
    • Organizer
      日本臨床分子医学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-10
    • Related Report
      2010 Final Research Report
  • [Presentation] Overexpression of Smad1 resulted inremarkable glomerulosclerosis in Diabetic mice2009

    • Author(s)
      Takeshi Matsubara, et. al.
    • Organizer
      Renal Week 2009
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2009-10-29
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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