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Development of specific inhibitors smooth muscle cell-derived migration factor (SDMF) and their clinical application

Research Project

Project/Area Number 05557048
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionYamagata university (1994)
Chiba University (1993)

Principal Investigator

SAITO Yasushi  Yamagata University. School of Medicine. Professor, 医学部, 教授 (50101358)

Co-Investigator(Kenkyū-buntansha) 佐伯 隆生  (株)エーザイ研究所, 主任研究員
篠宮 正樹  千葉大学, 医学部, 助手 (50206116)
森崎 信尋  千葉大学, 医学部, 講師 (40174411)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1994: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordssmooth muscle cell derived / migration factor (SDMF) / Smooth muscle cells / atherosclerosis / cytokines / calcium antagonist / phenotype
Research Abstract

1. Purification of smooth muscle cell derived migration factor (SDMF) : SDMF was purified from 100L of conditioned media dirived from cultured rat aortic smooth muscle cells (SMC) through four steps of columns. The molecular weight and isoelectric point of isoelectric point of SDMF were 58KD and PH 10.0, respectively. SDMF was specific to SMC and migration (no mitogenic activity) . The maximal activity of SDMF was four-fold that of PDGF.
2. Cloning of SDMF gene : Purified SDMF was subjected to acid break down, producing the fragments of 35KD and 25KD.N-terminus of 35KD fragment was being blocked. 10 amino acids of N-terminus of 25KD fragment were detected and cDNA probes were synthesized from this amino acid information. The SDMF gene cloning is now in progress.
3. Regulation of SDMF expression : SDMF was expressed in synthetic SMC but not in contractile SMC.Of synthetic phenotype, SMC derived from atheromatous intima expressed more SDMF than SMC derived from normal media by 1.5 fold. Among various cytokines tested, only TGF-beta inhibited expression of SDMF.
4. Inhibitors of SDMF : Among endogenous cytokines tested. PDGF-AA,TGF-beta, and C-type natriuretic peptide inhibited migration of SMC stimulated by SDMF in a concentration dependent manner.
Among calcium antagonists tested, only nifedipine was inhibitory of SDMF activity.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Morisaki N, Takahashi K, Shina R, Zenibayashi M, Otabe M, Yoshida S, Saito Y.: "Platelet-Derived Growth Factor Is a Potent Stimulator of Expression of Intercellular Adhesion Molecule-1 in Human Arterial Smooth Muscle Cells" Biochem Biophys Res Commun. 200. 612-618 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kanzaki T, Shinomiya M, Ueda S, Morisaki N, Saito Y, Yoshida S.: "Enhanced arterial intimal thickening after balloon catheter injury in diabetic animals accompanied by PDGF β-receptor overexpression of aortic media." Eur J Clin Invest. 24. 377-381 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shinomiya M, Tashiro J, Saito Y, Yoshida S, Furuya M, Oka N, Tanaka S, Kagawa K, Matsuo H.: "C-type natruretic peptide inhibits intimal thickening of rabbit carotid artery after balloon catheter injury" Biochem Biophys Res Commun. 205. 1051-1056 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morisaki N, Yokota K, Takahashi K, Otabe M, Saito Y, Yoshida S, Ueda S.: "Role of phospholi;ase A2 in expression of the scavenger pathway in cultured aortic smooth muscle cells stimulated with phorbol 12-myristate 13-acetate" Biochem J. 303. 247-253 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Inaba T, Yamada N, Gotoda T, Saito Y, Yoshida S, Yazaki Y.: "Expression of C-FMS on smooth muscle cells isolated from experimental arteriosclerosis" J Atheroscler & Thromb. 1. S22-S28 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koyama N,Harada K,Yamamoto A,Morisaki N,Saito Y,Yoshida S.: "Purification and characterization of an autocrine migration factor for vascular smooth muscle cells (SMC) , SMC-derived migration factor" J Biol Chem. 268. 13301-8 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Koyama N,Watanabe S,Tezuka M,Morisaki N,Saito Y,Yoshida S.: "Migratory and proliferative effect of platelet-derived growth factor in rabbit endothelial cells : Evidence of an autocrine pathway of platelet-derived growth factor" J Cell Physiol. 158. 1-6 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morisaki N,Takahashi K,Shina R,Zenibayashi M,Otabe M,Yoshida S,Saito Y.: "Platelet-Derived Growth Factor Is a Potent Stimulator of Expression of Intercellular Adhesion Molecule-1 in Human Arterial Smooth Muscle Cells" Biochem Biophys Res Commun. 200. 612-618 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kanzaki T,Shinomiya M,Ueda S,Morisaki N,Saito Y,Yoshida S.: "Enhanced arterial intimal thickening after balloon catheter injury in diabetic animals accompanied by PDGF beta-receptor overexpression of aortic media" Eur J Clin Invest. 24. 377-381 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shinomiya M,Tashiro J,Saito Y,Yoshida S,Furuya M,Oka N,Tanaka S,Kagawa K,Matsuo H.: "C-type natruretic peptide inhibits intimal thickening of rabbit carotid artery after ballon catheter injury" Biochem Biophys Res Commun. 205. 1051-1056 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morisaki N,Yokote K,Takahashi K,Otabe M,Saito Y,Yoshida S,Ueda S: "Role of phospholi ; ase A2 in expression of the scavenger pathway in cultured aortic smooth muscle cells stimulated with phorbol 12-myristate 13-acetate" Biochem J. 303. 247-253 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] MorisakiN,TakahashiK.Shlna R,Zonibayashi M,Otabe M,Yoshida S,Saito Y: "Platelet derived growth factor is a potent stimulator of ecpression of intercellular adhesion moleculet in human arterial smooth muscle cells" Biochem Biophys Res Commun. 200. 612-618 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kanzaki T,Shinomiya M,Ueda S,Morisaki N,Saito Y,Yoshida S: "Enhanced arterial intirval thickening after ballon catheter injury in diabetic animals accompanied by PDGF-β-receptor over expression of aortic media" Eur J.Clin Invest. 24. 377-181 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinomiya M,Tashiro J,Saito Y,Yoshida S,Furuya M,Oka N,Tanaka,S,Kagawa K,Matuo H: "C-type natriuretic peptide inhibits intirval thickoning of rabbit carotid artery after ballon catheter injury" Biochem Biophys Res Commun. 205. 1051-1056 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Morisaki,N,Yokote K,Takahashi K,Otabe M,Saito Y,Yoshida S,Ueda S: "Role of phospholipase A_2 in expression of the scavenger pathuray in caltured aortic smooth muscle cells stimulated with phorbol 12-myristate 13-acetate" Biochem J. 303. 247-253 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Inaba T,Yamada N,Gotoda T,Saito Y,Yoshida S,Yazaki Y: "Expression of c-fms on smooth muscle cells isolated from experimental arteriosclerosis" J Atheroscler & Thromb. 1. S22-S28 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Koyama N,Harada K,Yamamoto A,Morisaki N,Saito Y,Yoshida S: "Purification and characterization of an autocrine migration factor for vascular smooth muscle colls(SMC),SMC-derived migration factor" J Biol Chem. 268. 13301-13308 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Koyama N,Watanabe S,Tezuka M,Morisaki N,Saito Y,Yoshida S: "Migratory and proliferative effect of platelet-derived growth factor in rabbit retinal endothelial alls:Evidence of an autocrine pathway of platdet-derived growth factor" J Cell Physiol. 158. 1-6 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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