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Roles of Matrix Metalloproteinases in wound healing and neovascuarization

Research Project

Project/Area Number 09670220
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

OKADA Akiko  Univ.of Tokyo, Inst.of med.Sci., Assistant Prof., 医科学研究所, 助手 (00233320)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordswound healing / neovascularization / matrix metalloproteinase / MMP inhibitor / skin / knockout mice / ラット / 生理的インヒビター
Research Abstract

Skin wound healing depends on cell migration and extracellular matrix remodeling. Both processes, which are necessary for reepithelization and restoration of the underlying connective tissue, are believed to involve the action of extracellular proteinases. We screened cDNA libraries and found that six matrix metalloproteinase genes were highly expressed during rat skin wound healing.
GelatinaseA (GelA) and membrane-type 1 matrix metalloproteinase (MT1-MMP) transcripts were expressed in stromal cells. The detection of high levels of the mature GelA form in the granulation tissue but not in the regenerating epidermis, suggest that MT1-MMP and GelA contribute to the restoration of connective tissue and neovascularization during rat skin wound healing. Furthermore, we showed that TIMP-2 is necessary for activation of pro-GelA by MT1-MMP using agarose beads model. We now make knock-out mice of MT1-MMP gene. Already we have obtained GelA knock-out mice, and we are under studying on the differences of wound healing and neovascular process between normal mice and knock-out mice. We also study on the effect of synthetic MMP inhibitor to wound healing process and/or neovascularization.

Report

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

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Okada A: "Expression of matrix metalloproteinases during rats skin wound healing : evidence that mem brane-type-1 matrix metalloproteinase (MT1-MMP) is a stromal activator of pro-gelatinase A" J. Cell Biol.137. 67-77 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada A: "Matrix metalloproteinases as stromal effectors of human carcinoma progression : therapeutic implications." Matrix Biol.15. 535-541 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada A: "Rat stromelysin 3 : cDNA cloning from skin healing wound, activation by furin, and expression in rat tissues." Gene. 185. 187-193 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada A: "TIMP-2 Promotes Activation of Progelatinase A by Membrane-type 1 Matrix Metalloproteinase Immobilized on Agarose Beads" J.Biol.Chem.273. 16098-16103 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada A: "Expression and degeneration of tenascin-C in human lung cancers" Br.J.Cancer. 77. 98-102 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada A., Tomasetto C., Luts Y., Rio M.C., Bellocq J.P., Basset P.: "Expression of matrix metalloproteinases during rat skin wound healing : evidence that membrance-type-1 matrix metalloproteinase (MT1-MMP) is a stromal activator of pro-gelatinase A." J.Cell Biol.137 :. 67-77 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Basset P., Okada A., Chenard M.P., Kannan R., Stoll I., Anglard P., Bellocq J.P/.Rio M.C.: "Matrix metalloproteinases as stromal effectors of human carcinoma progression : therapeutic implications." Matrix Biol.15 :. 535-541 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada A., Saez S., Misumi Y., Basset P.: "Rat stromelysis 3 : cDNA cloning from skin healing wound, activation by furin, and expression in rat tissues." Gene. 185 :. 187-193 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kinoshita T,Sato H,Okada A,Ohuchi E,Imai K,Okada Y,Seiki M: "Promotes Activation of Progelatinase A by Membrane-type 1 Matrix Metalloproteinase immobilized on Agarose Beads." J Biol Chem. 273 :. 16098-16103 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kusagawa, H., Onoda, K., Namikawa, S., Yada, I., Okada, A., Yashida, T., Sakakura, T.: "Expression and degeneration of tenascin-C in human lung cancers." Br.J.Cancer. 77 :. 98-102 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kinoshita T: "TIMP-2 Promotes Activation of Progelatinase A by Membrane-type 1 Matrix Metalloproteinase Immobilized on Agarose Beads" J.Biol.Chem.273. 16098-16103 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kusagawa H: "Expression and degeneration of tenascin-C in human lung cancers" Br.J.Cancer. 77. 98-102 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akiko Okada: "Expression of matrix metalloproteinases during rat skin wound healing:evidence that membranetype-1.matrix metalloproteinase(MT1-MMP)is a stromal actiyator of pro-gelatinase A." J.Cell Biol.137. 67-77 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akiko Okada: "Rat stromelysin 3:cDNA cloning from skin healing wound,activation by furin,and expression in rat tissues." Gene. 185. 187-193 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Paul Basset: "Matrix metalloproteinases as stromal effectors of human carcinoma progression:therapeutic implications." Matrix Biol.15. 535-541 (1997)

    • Related Report
      1997 Annual Research Report

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

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