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Pathogenesis and molecular mechanisms of arteral restenosis

Research Project

Project/Area Number 06454287
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionGunma University School of Medicine (1995)
The University of Tokyo (1994)

Principal Investigator

NAGAI Ryozo  Gunma University School of Medicine 2nd Dept of Int Med, Professor, 医学部, 教授 (60207975)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tetsuya  Gunma University School of Medicine 2nd Dept of Int Med, Assistant, 医学部, 助手 (10272238)
ARAI Masashi  Gunma University School of Medicine 2nd Dept of Int Med, Assistant, 医学部, 助手 (60270857)
中原 賢一  東京大学, 医学部(病), 医員
山崎 力  東京大学, 医学部(病), 助手 (60251245)
黒尾 誠  東京大学, 医学部(病), 医員
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsRESTENOSIS, / SMOOTH MUSCLE, / MYOSIN, / SM1 / 2 GENE, / SMemb GENE, / TRANSCRIPTION FACTOR, / PTCA / 転写因子 / ミオシン重鎖 / 遺伝子転写 / 形質変換
Research Abstract

We previously demonstrated that rabbit and rat smooth muscles contain at least three types of MHCs ; SM1(204kDa), SM2(200kDa)and SMemb(200kDa). SM1 and SM2 are two smooth muscle specific MHC isoforms arising from a singlegene, and SMemb is a third type of MHC isoform abundantly expressed in embryonic aortas. The expression of three MHC isoforms is developmentallyregulated.
The presence of developmentallyregulated MHC isoforms in vascular smooth muscles provides importantmoleculartools to investigate the molecularmechanism underlying vascular diseases. We first demonstrated that the developmentalregulation of myosin heavy chain expression occurs in proliferating smooth muscle cells after percutaneous angioplasty(PTCA) ; SMemb was reexpressed and SM2 was downregulated. We therefore characterized the promoter region of the SM1/2 and SMemb genes. In this study, we identified an important cis element for the SMemb gene and a transcription factor, BTEB-2, which coordinately regulate the SMemb gene.
We furthermore characterized SM1/2 gene which is most specifically expressed in smooth muscles. SM1/2 gene harbors two CCTCCC elements-80 bp upstream of the transcription initiation site. These elements play a basic role for SM1/2 gene transcription but does not necessarily regulate smooth muscle-specific expression.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kurihara Y et al: "Aortic Arch malformation and ventricular septal defect in mice deficient in endothelin-1." J Clin Invest. 96. 293-300 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takewaki S et al: "Activation of Na^+-H^+ antiporter (NHE-1) gone, expression during growth, hypertrophy and proliferation of the rabbit cardio-vascular system" J. mol. Cell. Cardiol. 27. 729-742 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okamoto E. et: "Diversity of the synthetic-state smooth muscle cells proliferating in mechanically and hemodynamically injured arteries" Lab. Invest. 74. 120-128 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe M et al.: "Structure and characterization of the 5' flanking region of the mouse smooth muscle myosin heavy chain gene" Circ Res. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki T et al: "A novel biochsmical diagnostic method for aortic dissection" Circulation. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki T, Nagai R, et al: "Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells; use of retinoic acid and antisense against the central nervoussystem-specific POU transcription factor Brn-2." Circulation Res. 78. 395-404 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe M, Nagai R et al.: "Tandem elements of CCTCCC are required for the cell-type-specific expression of the mouse smooth muscle myosin heavy chain gene (SM1/2) promoter." Circulatin Res. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takewaki S,Kuro-o M,Hiroi Y,Watanabe M,Noguchi T,Nakahara K,Aikawa M,Manabe I,Ohkubo A,Yazaki Y,Nagai R.: "Activation of Na^+-H^+antipoter(NHE-1)gene expression during growth, hypertrophy and proliferation of the rabbit cardiovascular system" J.Mol.Cell Cardiol.27. 729-742 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kimura K,Nagai R,Sakai T,Aikawa M,Kuro-o M,Kobayashi N,Shirato I,Inagami T,Oshi M,Suzuki N,Oba S,Mise N,Tojo A,Hirata Y,Goto A,Yazaki Y,Omata M.: "Diversity and variability of smooth muscle phenotypes of renal arterioles as revealed by myosin isoform expression." Kidney Int. 48. 372-382 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kurihara Y,Kurihara H,Oda H,Maemura K,Nagai R,Ishikawa T,Yazaki Y.: "Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1." J Clin Invest. 96. 293-300 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shimada H,Shimizu T,Kuwayama H,Suzuki M,Nagai R,Morii H: "Immunocytochemical localization of 155 kDa myosin light chain kinase and myosin heavy chain in bovine brain." Brain Res. 682. 212-214 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okamoto E,Suzuki T,Aikawa M,Jun Fujii, Kuro-o M,Nakahara K,Yazaki Y,Nagai R.: "Diversity of the synthetic-state smooth muscle cells proliferating in mechanically and hemodynamically injured rabbit arteries." Lab Invest.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroi J,Kimura K,Sakai T,Aikawa M,Kuro-o M,Kobayashi N,Shirato I,Inagami T,Oshi M,Suzuki N,Oba S,Mise N,Tojo A,Hirata Y,Goto A,Yazaki Y,Omata M,Nagai R.: "Expression of a nonmuscle myosin heavy chain in glomerular cells differentiates various types of glomerular disease in rats." Kidney Int. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe M,Sakomura Y,Aikawa M,Sakomura Y,Kuro-o M,Suzuki T,Yazaki Y,Nagai R.: "Structure and characterization of the 5'-flanking region of the mouse smooth muscle myosin heavy chain (SM1/2) gene." Circulation Res. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki T,H-S Kim, Kurabayashi M,Hamada H,Fujii H,Aikawa M,Watanabe M,Yazaki Y,Nagai R.: "Preferential differetiation of P19 mouse embryonal carcinoma cells into smooth muscle cells ; using retinoic acid and antisense against the CNS-specific POU transcrioption factor Brn-2." Circulation Res. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki J,Isobe M,Aikawa M,Kawauchi M,Shiojima I,Kobayashi N,Tojo A,KimuraK,Nishikawa T,Sakai T,Sekiguchi M,Yazaki Y,agai R.: "Nonmuscle and smooth muscle myosin heavy chain expression in rejected cardiac allograft-a study in rat and monkey models." Circulation.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki T,Katoh H,Suzuki S,Ohtaki E,Watanabe M,Yazaki Y,Nagai R.: "A novel biochemical diagnostic method for aortic dissection-the results of a prospective study using an immunoassay of smooth muscle myosin heavy chain." Circulation. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki T, Nagai R et al: "Preferential differentiation of P19 mouse embryonal carcinoma cells into smooth muscle cells ; use of retinoic acid and antisense against the central nervous system-specific POU transcription tactor Brn-2." Circulation Res. 78. 395-404 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe M, Nagai R et al.: "Tandem elements of CCTCCC are required for the celltype-specific expression of the mouse smooth muscle myosin heavy chain gene (SM1/2) promoter." Circulatin Res. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Kojima M.,et al: "Angiotensin II receptor antagonist TCV 116 regresses hypertensive left ventricular hypertrophy in vivo and inhibits intracellular signaling pathway of stretch-medioted cardiomyocyte hypertrophy in vitro" Circulation. 89. 2204-2211 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kurihara Y.,et al: "Disruption of mouse endothelin-1 gene results in lethality and craniofacial anomaly in homozygotes and elevated blood pressure in heterxygotes" Nature. 368. 703-710 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka T.,et al: "Gene linkage analyses of romano-ward syndrome (PWS) in 13 Japanese familes." Human Genetics. 94. 380-384 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kuroo M.,et al: "Salt-sensitinve hypertension in transgenic mice overexpressing Sodium-proton exchanger." Circulation Resarch. 76. 148-153 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Katoh H.,et al: "Diagnosis of aortic dissection by Immunoassay for circalating smooth muscle myosin." Lancet. 345. 191-192 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagai R.,et al: "The Adapted Heart." Raven Press. New York, 520 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shiojima I.,et al: "Diastolic relaxation of the heart" Kluwer Academic Publisher,Boston, 624 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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