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2012 Fiscal Year Final Research Report

Development of Specific Biomarker and Molecular Targeting Therapy for Diabetic Nephropathy by RAS-independent Pathway

Research Project

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Project/Area Number 22390169
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

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)

Co-Investigator(Kenkyū-buntansha) 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)
NAGAI Kojiro  徳島大学, 病院, 講師 (40542048)
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 (00432401)
TOMINAGA Tatsuya  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80425446)
Project Period (FY) 2010 – 2012
KeywordsBMP4 / 糖尿病性腎症 / Smad1
Research Abstract

BMP4 directly regulated Smad1 signaling in vitro. Both BMP4 and phosphorylated Smad1 were expressed in association with mesangial matrix hyperplasia in diabetic kidney. BMP4 knock-in transgenic mice showed typical mesangial matrix increase as well as BMP4 expression after induction by tamoxifen. On the other hand, BMP4 knock-out (BMP4(+/-)) mice showed amelioration of glomerular matrix hyperplasia induced by streptozotocin. Furthermore, neutralizing antibody for BMP4 normalized glomerular matrix hyperplasia and phosphorylated Smad1 expression in glomeruli of diabetic mice. These results suggest that BMP4/Smad1 signaling plays the critical pathogenetic role for diabetic nephropathy.

  • Research Products

    (12 results)

All 2013 2012 2011 2010

All Journal Article (12 results) (of which Peer Reviewed: 12 results)

  • [Journal Article] Polymorphism in the human matrix Gla protein gene is associated with the progression of vascular calcification in maintenance hemodialysis patients2013

    • Author(s)
      Yoshikawa K, Abe H, Tominaga T, Nakamura M, Kishi S, Matsuura M, Nagai K, Tsuchida K, Minakuchi J, Doi T
    • Journal Title

      Clin Exp Nephrol.

    • DOI

      DOI:10.1007/s10157-013-0785-9

    • Peer Reviewed
  • [Journal Article] Acute glomerulonephritis in an immunocompetent elderly woman after contact with a child who had been diagnosed as erythema infectiosum2012

    • Author(s)
      Kishi S, Yamada S, Kishi F, Shibata E, Matsuura M, Nagai K, Mima A, Abe H, Doi T.
    • Journal Title

      Intern Med

      Volume: 51 Pages: 2197-2201

    • DOI

      DOI:10.2169/internalmedicine.51.7919

    • Peer Reviewed
  • [Journal Article] Scleraxis modulates bone morphogenetic protein 4 (BMP4)-Smad1 protein-smooth muscle α-actin (SMA) signal transduction in diabetic nephropathy.2012

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

      Journal of Biological Chemistry

      Volume: 287 Pages: 20430-20442.

    • DOI

      DOI:10.1074/jbc.M111.275610.

    • Peer Reviewed
  • [Journal Article] SOX9 protein induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy.2011

    • 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 K, Doi T
    • Journal Title

      Jbiol Chem

      Volume: 286 Pages: 32162-32169.

    • DOI

      DOI:10.1074/jbc.M111.244541.

    • Peer Reviewed
  • [Journal Article] An autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with intestinal bleeding in chronic renal failure2011

    • Author(s)
      Mima A, Shiota F, Matsubara T, Iehara N, Akagi T, Abe H, Nagai K, Matsuura M, Murakami T, Kishi S, Araoka T, Kishi F, Kondo N, Shigeta R, Yoshikawa K, Kita T, Doi T, Fukatsu A
    • Journal Title

      Ren Fail.

      Volume: 33 Pages: 622-625

    • DOI

      DOI:10.3109/0886022X.2011.585730

    • Peer Reviewed
  • [Journal Article] MPO-ANCA-positive anti-glomerular basement membrane antibody disease successfully treated byplasma exchange and immunosuppressive therapy.2011

    • Author(s)
      Murakami T, Nagai K, Matsuura M, Kondo N, Kishi S, Araoka T, Kishi F, Sakiyama T, Mima A, Bando Y, Abe H, Doi T.
    • Journal Title

      Ren Fail

      Volume: 33 Pages: 626-631

    • DOI

      DOI:10.3109/0886022X.2011.581401.

    • Peer Reviewed
  • [Journal Article] Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy.2011

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

      J Biol Chem.

      Volume: 286 Pages: 20109-20116

    • DOI

      DOI:10.1074/jbc.M110.179382.

    • Peer Reviewed
  • [Journal Article] Activation of Src mediates PDGF-induced Smad1 phosphorylation and contributes to the progression of glomerulosclerosis in glomerulonephritis.2011

    • 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 Pages: e17929.

    • DOI

      DOI:10.1371/journal.pone.0017929.

    • Peer Reviewed
  • [Journal Article] Mixed connective tissue disease developing into MPO-ANCA-positive polyangiitis2011

    • Author(s)
      Murakami T, Endo S, Moriki T, Doi T, Matsumoto Y.
    • Journal Title

      Intern Med.

      Volume: 50 Pages: 591-595

    • DOI

      DOI:org/10.2169/internalmedicine.50.3958

    • 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 Pages: 531-541

    • URL

      http://www.hh.um.es/Abstracts/Vol_26/26_4/26_4_531.htm

    • Peer Reviewed
  • [Journal Article] rophoblast glycoprotein: possible candidate mediating podocyte injuries in glomerulonephritis2010

    • Author(s)
      Murakami T, Abe H, Nagai K, Tominaga T, Takamatsu N, Araoka T, Kishi S, Takahashi T, Mima A, Takai Y, Kopp JB, Doi T
    • Journal Title

      Am J Nephrol.

      Volume: 32 Pages: 505-521

    • DOI

      DOI:10.1159/000321366.

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

    • 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 Pages: 209-218.

    • DOI

      DOI:10.1007/s10059-010-0109-9.

    • Peer Reviewed

URL: 

Published: 2014-08-29   Modified: 2014-09-05  

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