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Basic study for the treatment of inflammatory skin diseases using the regulation of gelatinolytic activities.

Research Project

Project/Area Number 17591158
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionChiba University

Principal Investigator

KOBAYASHI Takashi  Chiba University, Clinical biology of Extracellular Matrix/Dermatology, Lecturer, 医学部附属病院, 講師 (90234830)

Co-Investigator(Kenkyū-buntansha) WACHI Hiroshi  Hoshi Pharmaceutical College, Clinical chemistry, Assistant Professor, 薬学部, 助教授 (50318614)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsgelatinase / inflammation / matrix metalloproteinase / caspase / involucrin / leptomycin B / RNA interference / decoy oligonucleotide / 角化 / 創傷治癒 / MMP-9 / TIMP-2 / KRE-M9
Research Abstract

Gelatinolytic activities by gelatinases, matrix metalloproteinase (MMP)-2 and MMP-9, with the inhibitions by tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 have been shown to play important roles in the inflammatory skin diseases. We have recently found the novel KRE-M9 element to which our designated differentiation repressing factor (DRF)-1 binds in the MMP-9 promoter.
1. RNA interference for MMP-2 and MMP-9
Caspase 3/7, 8, and 9 activities, which have been shown to be responsible for inflammation as well as for apoptosis, were measured on cells in culture after the RNA interference for MMP-2 or for MMP-9. As a result, caspase-3/7 activity was especially reduced by each interference.
2. Regulation of MMP-9 expression through KRE-M9 element
Using decoy treatment for the KRE-M9 element on cells in culture, MMP-9 expression was induced, indicating the inhibitory activity of the KRE-M9 element. DRF-1 was purified from the nuclear extract by biotinylated KRE-M9 oligonucleotide and by streptavidine-Sepharose, and the nature of DRF-1 was analyzed. DRF-1 was fragmented by caspase-3/7 activity, which was induced by the stimulation for the differentiation of keratinocytes in the epidermis. RNA interference for DRF-1 enhanced the transcriptional activities not only for MMP-9, but also for involucrin, which is known to be the marker for the differentiation of keratinocyte.
3. Treatment with leptomycin B (LMB) known as the regulater for trafficking the nuclear export of some proteins
he addition of LMB for the cells in culture reduced MMP-9 transcription, whereas it induced the TIMP-2 one. The topical application of LMB to mouse suppressed the inflammation after ultraviolet B irradiation, and it also showed the effect for the improvement of wound healing.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (5 results)

All 2005

All Journal Article (5 results)

  • [Journal Article] Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation.2005

    • Author(s)
      Kobayashi T., Shinkai H.
    • Journal Title

      J. Invest. Dermatol. 124

      Pages: 331-337

    • NAID

      40006752039

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Laminin α 3LG4 module induces keratinocyte migration : Involvement of matrix metalloproteinase-9.2005

    • Author(s)
      Momota Y., Suzuki N., Kasuya Y., Kobayashi T., Mizoguchi M.et al.
    • Journal Title

      J. Recept. Sig. Transd. 25

      Pages: 1-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Leptomycin B redices matrix metalloproteinase-9 expression and suppresses cutaneous inflammation.2005

    • Author(s)
      Kobayashi T., Shinkai H.
    • Journal Title

      J. Invest. Dermatol. 124

      Pages: 331-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lamininα3LG4 module induces keratinocyte migration : Involvement of matrix metalloproteinase-9.2005

    • Author(s)
      Momota Y., Suzuki N., Kasuya Y., Kobayashi T., Mizoguchi M., et al.
    • Journal Title

      J. Recept. Sig. Transd. 25

      Pages: 1-17

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation.2005

    • Author(s)
      Kobayashi T., Shinkai H.
    • Journal Title

      J Invest Dermatol 124

      Pages: 331-337

    • NAID

      40006752039

    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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