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Molecular mechanism of phenotypic modulation of reral cells in progressive reral disease

Research Project

Project/Area Number 09671165
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionOsaka University

Principal Investigator

MORIYAMA Toshio  Osaka University, School of Health and Sport Sciences, Assistant Professor, 健康体育部, 講師 (30283815)

Co-Investigator(Kenkyū-buntansha) MIWA Takeshi  Osaka University, Genoma Information Research Center, Associate Professor, 遺伝実験情報施設, 助教授 (20174229)
IMAI Enyu  Osaka University Medical School, Research Assistant, 医学部, 助手 (00223305)
ANDO Akio  Osaka University, School of Health and Sport Sciences, Professor, 健康体育部, 教授 (00028656)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsin vivo promoter analysis / myofibroblast / habu-venom / glomerulonephritis / phenotypic modulation / GArG element / smooth muscle alpha actin / transgenic mouse
Research Abstract

Activation of glomerular mesangial cells is one of the early, important features of progressive glomerular disease.Smooth muscle alpha-actin (SMalphaA) is an excellent marker of activated mesangial cells.We examined in vivo promoter analysis of the SMalphaA gene utilizing transgenic mice harboring different promoter regions of the SMalphaA gene fused to chloramphenicol acetyl transferase (CAT).CAT activities were tested in primary cultured mesangial cells, and in glomerular legions of habu-venom glomerulonephritis.DNA sequence -891 to +3828, which contains exon 1, intron 1, and the first 14 bp of exon 2 in addition to the 5'-flanking sequence of the SMalphaA gene, induced high levels of transcription in activated mesangial cells in in vivo habu-venom glomerulonephritis and in cultured mesangial cells derived from transgenic mice.DNA region -891 to -124 was a positive element in mesangial cells derived from transgenic mice.Deletions (3316 bp or 137 bp) in intron 1 reduced transcription to undetectable levels.The 137 bp sequence is highly conserved among several species, containing one CArG box element, which is one of the key motifs for transcriptional activation of contractile-related proteins.In vitro transfection analysis failed to demonstrate these positive effects of intron 1 and region -891 to -124.Further analysis of the intron 1 region (+1088 to +1224), including the CArG box element, will be of great value in understanding the molecular mechanisms of mesangial activation.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Kawad N,Moriyama T,Ando A,Koyama T,Hori M,Miwa T,Imai E,: "The role of infrom I in Smooth miscle α actin transcriptional regulation in activated nesangial alls in vivo." Kidney International. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawada N,Moriyama T,Ando A,Koyama T,Hori M,and Imai E.: "The role of intreal in smooth muscle alpha actin transcriptional regulation in activated mesangial cells in vivo" Kidney International. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawada N,Moriyama T,Ando A,Kayama T,Hori M,Miwa T,Imai E: "The role of intron 1 in smooth muscle α-actin transcriptional regulation in activated mesangial cells in vivo" Kidney International. 印刷中.

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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