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Effect of CKI overexpression on Smooth Muscle Cell Growth

Research Project

Project/Area Number 12671094
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionHokkaido University

Principal Investigator

URASAWA Kazushi  Hokkaido Univ. Grad. School of Med., Lecturer, 大学院・医学研究科, 講師 (00280850)

Co-Investigator(Kenkyū-buntansha) FUJII Satoshi  Hokkaido Univ. Medical Hospital, Lecturer, 医学部付属病院, 講師 (90291228)
OKAMOTO Hiroshi  Hokkaido Univ. Medical Hospital, Lecturer, 医学部付属病院, 講師 (50260394)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsCDK inhibitor / Cell cycle / Smooth Muscle / 遺伝子治療 / 細胞増殖 / 血管平滑筋細胞
Research Abstract

Vascular smooth muscle cells (VSMCs) exhibit enhanced proliferation under mitogenic stimulation and accumulate in neointima after arterial injury. The cell cycle progression is positively regulated by cyclin/cyclin-dependent kinase (CDK) complex, and negatively controlled by p21 family. P57kip2 is one of the members of p21 family and its distribution is relatively limited to terminally differentiated tissues, including muscle. However, p57kip2 contribution to VSMC proliferation remains scarcely unknown. In this study, we investigated the role of p57kip2 in VSMC proliferation, in combination with other cell cycle related proteins. VSMCs were G0 arrested by serum deprivation, followed by mitogenic stimulation with growth medium, and harvested at every four hour. The phenotype of immature VSMCs didn't differentiate even after mitogenic deprivation. The protein levels of p57kip2 and p27kip1 diminished by mitogenic stimulation, in correlation with the upregulation of cyclin-D, -E and CDK2 protein amount and their kinase activities, resulting in the phosphorylation of retinoblastoma (Rb) protein family members, p107 and p130. Immunoprecipitation revealed that p27kip1 could associate with cyclin-D1, but did not inhibit its activity. On the contrary, p57kip2 could bind to cyclin-D1, and overexpressed p57kip2 prevented the phosphorylation of Rb family, probably due to canceling the cyclin-D1 (and/or cyclin-E) kinase activation. In conclusion, p57 decline is likely to be the key event for initiation of immature VSMCs proliferation. These results suggested that spplemental overexpression of p57kip2 could be a powerful strategy to prevent the development of intimal hyperplasia after arterial injury.

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Hidetsugu Sakai: "Distal shower embolization during directional coronary atherectomy and stenting for diffuse stenosis of right coronary artery"Circulation Journal. 68(3)(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naotsugu Oyama: "Side branch protection with hydrophilic polymer coated guide wire during cutting balloon angioplasty of a bifurcated lesion"Japanese Heart Journal. 44(4)(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hidetsugu Sakai: "A plaque core invasion into the coronary artery lumen after direct stenting"Interventional Cardiology. 68(3)(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naotsugu Oyama: "A case of accordion phenomenon accompanied by severe transmural myocardial ischemia"Japanese Heart Journalogy. 43(1). 49-54 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazushi Urasawa: "Vascular Smooth Muscle Cell Proliferation is Effectively Suppressed by the Non-specific Growth Factor Inhibitor Suramin"Japanese Heart Journalogy. 42(2). 221-233 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takanori Ogawa: "Effects of Nonionic Contrast Media on Platelet Aggregation : Assessment by Particle Counting with Laser-Light Scattering"Japanese Heart Journal. 42(1). 115-124 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hidetsugu Sakai, Kazushi Urasawa, Naotsugu Oyama, Akira Kitabatake: "Distal shower embolization during directional coronary atherectomy and stenting for diffuse stenosis of right coronary artery : A case report - Current limitation of intravascular ultrasonography to evaluate fragile plaque."Circulation Journal. 68(3) (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naotsugu Oyama, Kazushi Urasawa, Hidetsugu Sakai, Akira Kitabatake: "Side branch protection with hydrophilic polymer coated guidewire during cutting balloon angioplasty of bifurcated lesion"Japanese Heart Journal. 44(4) (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hidetsugu Sakai, Kazushi Urasawa, Naotsugu Oyama, Akira Kitabatake: "A plaque core invasion into the coronary artery lumen after direct stenting"A case report. Japanese Journal of Interventional Cardiology. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naotsugu Oyama, Kazushi Urasawa, Hidetsugu Sakai, Akira Kitabatake: "A case of accordion phenomenon accompanied by severe transmural myocardial ischemia"Japanese Heart Journal. 43(1). 49-54 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazushi Urasawa, Satoshi Kaneta, Noritsugu Nakano, Takahiko Saito, Hidetsugu Sakai, Chika Takagi, Yasushi Takagi, Hiroyuki Sugiki, Akira Kitabatake: "Vascular Smooth Muscle Cell Proliferation is Effectively Suppressed by the Non-specific Growth Factor Inhibitor Suramin"Japanese Heart Journal. 42(2). 221-233 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takanori Ogawa, Satoshi Fujii, Kazushi Urasawa, Akira Kitabatake: "Effects of Nonionic Contrast Media on Platelet Aggregation : Assessment by Particle Counting with Laser-Light Scattering"Japanese Heart Journal. 42(1). 115-124 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lai NC: "Intracoronary delivery of adenovirus encoding adenylyl cyclase VI"Circulation. 102(19). 2396-2401 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takanori Ogawa: "Effects of nonionic contrast media on platelet aggregation"Japanese Heart Journal. 42(1). 115-124 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazushi Urasawa: "Vascular smooth muscle cell proliferation is effectively suppressed by the non-"Japanese heat Journal. 42(1). 221-233 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akira Kitabatake: "Non-invasive assessment of left ventricular diastolic function by color M-"Journal of Mechanics in Medicine and Biology. 1(2). 97-105 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masakazu Yamagishi: "Coronary disease morphology and distribution determined by quantitative"Circulation Journal. 66(8). 735-740 (2002)

    • Related Report
      2002 Annual Research Report

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

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