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The Study of Progressive Factors to Developing Glomerular Injury

Research Project

Project/Area Number 12470210
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  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (60183498)

Co-Investigator(Kenkyū-buntansha) MIZUNO Akira  The University of Tokushima, Medical School Hospital, Instructor, 医学部附属病院, 助手 (80219641)
NOMA Yoshihiko  The University of Tokushima, Medical School Hospital, Assistant Professor, 医学部附属病院, 講師 (10218349)
KUWAJIMA Masamichi  The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (00205262)
TSUKAGUCHI Hiroyasu  The University of Tokushima, School of Medicine, Instructor, 医学部, 助手 (60335792)
石井 賢二  京都大学, 医学研究科, 助手 (00212811)
村上 尚  徳島大学, 医学部, 助手 (40210009)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
Keywordsmesangial cell / proliferation / Gas 6 / growth factor / warfarin / STAT3 / glomerulosclerosis / vitamin K / Axl / Gla化蛋白 / 増殖抑制 / 糸球体硬化症 / Erk
Research Abstract

Mesangial cell proliferation is a general characteristic of a variety of glomerular injuries. Growth arrest gene 6 (Gas 6) was one of vitamin K-dependent proteins, which was reported that the γ-carboxylation of Gas 6 is essential for its receptor-binding and growth-promoting activities in cells. The present study shows the role of Gas 6 for development of glomerular injury. Gas 6 is a new autocrine growth factor of mesangial cells. We examined the role of Gas 6/Axl in vivo in an experimental anti-Thy1 glomerulonephritis. The expression of Gas 6 was markedly increased in glomeruli in the model and the administration of warfarin significantly inhibited mesangial proliferation and the increased Gas 6 expression. The administration of Axl-extracellular domain (receptor for Gas 6) also inhibited mesangial cell proliferation. Gas 6 induced mesangial cell proliferation via latent transcription factor STAT3 in vitro and in vivo. To investigate these findings, we constructed Gas 6-/- mice and examined the role of it in accelerated nephrotoxic nephritis. Gas 6-/- mice showed less proteinuria, glomerular cell proliferation, glomerulosvlerosis and crescent formation than wild-type nephritis. These data indicate that Gas 6 contributes to glomerular injury and the progression of glomerular sclerosis.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] M.Yanagita: "Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis"American Journal of Pathology. 158(4). 1423-1432 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yanagita: "Gas6 induces mesangial cell proliferation via latent transcription factor STAT3"The Journal of Biological Chemistry. 276(45). 42364-42369 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yanagita: "Essential role of Gas6 for glomerular injury in nephrotoxic nephritis"J Clin Invest.. 110(2). 239-246 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Sano: "Blockade of platelet-derived growth factor receptor-beta pathway induces apoptosis of vascular endothelial cells and disrupts glomerular capillary formation in neonatal mice"Am J Pathol.. 161(1). 135-143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Hirata: "22-Oxacalcitriol prevents progressive glomerulosclerosis without adversely affecting calcium and phosphorus metabolism in subtotally nephrectomized rats"Nephrol Dial Transplant. 17(12). 2132-2137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yanagita: "Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis"American Journal of Pathology. 158(4). 1423-1432 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yanagita: "Gas6 induces mesangial cell proliferation via latent transcription factor STAT3."The Journal of Biological Chemistry. 276(45). 42364-42369 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yanagita: "Essential role of Gas6 for glomerular injury in nephrotoxic nephritis."J Clin Invest.. 110(2). 239-246 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Sano: "Blockade of platelet-derived growth factor receptor-beta pathway induces apoptosis of vascular endothelial cells and disrupts glomerular capillary formation in neonatal mice."Am J Pathol.. 161(1). 135-143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Hirata: "22-Oxacalcitriol prevents progressive glomerulosclerosis without adversely affecting calcium and phosphorus metabolism in subtotally nephrectomized rats."Nephrol Dial Transplant.. 17(12). 2132-2137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Yanagita: "Essential role of Gas6 for glomerular injury in nephrotoxic nephritis"J Clin Invest.. 110(2). 239-246 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Sano: "Blockade of platelet-derived growth factor receptor-beta pathway induces apoptosis of vascular endothelial cells and disrupts glomerular capillary formation in neonatal mice"Am J Pathol.. 161(1). 135-143 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Hirata: "22-Oxacalcitriol prevents progressive glomerulosclerosis with out adversely affecting calcium and phosphorus metabolism in subtotally nephrectomized rats"Nephrol Dial Transplant. 17(12). 2132-2137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Imabayashi: "Expression of basic helix-loop-helix proteins in the glomeruli"Clinical Nephrology. 55. 53-58 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Doi: "The contribution of mesangial cell proliferation to progressive glomerular injury"The Journal of Medical Investigations. 48(1,2). 1-4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Yanagita: "Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis"American Journal of Pathology. 158(4). 1423-1432 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Makibayashi: "A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis"American Journal of Pathology. 158(5). 1733-1741 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Yamamoto: "Development and prevenntion of advanced diabetic nephropathy in RAGE-overexpressing mice"The Journal of Clinical Investigation. 108(2). 261-268 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Yanagita: "Gas6 induces mesangial cell proliferation via latent transcription factor STAT3"The Journal of Biological Chemistry. 276(45). 42364-42369 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Murakami T: "Influence of the presence of OB-Re on leptin radio immunoassay"Journal of Endocrinology. 168. 79-86 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imabayashi T: "Expression of basic helix-loop-helix proteins in the glomeruli"Clinical Nephrology. 55. 53-58 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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