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The study of the gene regulation and the physiological functions of MMP-23 during ovarian follicle development

Research Project

Project/Area Number 16570106
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTokyo Medical and Dental University (2005)
Hokkaido University (2004)

Principal Investigator

OHNISHI Junji  Tokyo Med.Dent.Univ., Med.Res.Ins., Associate Prof., 助教授 (40261276)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOvary / Proteinase / Signal transduction / Gene regulation / Development & Differentiation / 顆粒膜細胞 / アポトーシス / マトリックスメタロプロテアーゼ / 排卵 / 卵胞刺激ホルモン / PI3キナーゼ / Akt
Research Abstract

Matrix metalloproteinase-23 (MMP-23), expressed predominantly in ovary and uterus, belongs to the MMP family that has been known to play a certain role in degrading and remodeling components of extracellular matrix (ECM). However, the physiological function of MMP-23 in the female reproductive organs remains yet to be clarified. During maturation of the follicle development in response to gonadotropin surge, expression levels of MMP-23 in granulosa cells were controlled under the state of differentiation of follicles. In the healthy follicles MMP-23 expression was repressed depending on the intracellular levels of cAMP, whereas, in the atretic follicles gene expression of MMP-23 was induced via de novo protein synthesis. When endogenous A-kinase or Akt expression was suppressed with the small interference RNA (siRNA) against rat A-kinase and Akt, gene repression of MMP-23 by cAMP was significantly inhibited. This result indicates the both kinases, activated by cAMP, are involved in the … More gene regulation of MMP-23 in the rat granulosa cells. Analysis of 1.5kb of the 5-flanking DNA sequence in the rat MMP-23 gene promoter revealed the absence of TATA box and Ets sequence in contrast to the other MMP family promoters. Detailed analysis of this promoter region has been under investigating to reveal the putative regulatory elements for cAMP-dependent repression and apotosis-dependent increment of MMP-23 gene expression.
To identify the physiological substrates for MMP-23 in the ovary, yeast two hybrid screening was carried out with human ovarian cDNA library using the catalytic domain of MMP-23 as a bait. As a result, interactive candidates were isolated including the ECM (fibronectin and fibrillin) and LTBP (latent TGF-β binding protein). From the binding analysis, MMP-23 interacts with fibrillin and LTBP via their EGF-like modules. TGF-β has been known as an indispensable factor for regulating the follicle maturation and active TGF-β must be released from the large complex of LTBP and ECM to exert its functions. Therefore, these results raise the possibility that MMP-23 might play a role in regulating the level of active TGF-β through modulating the ECM and LTBP in the ovarian follicles. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004

All Journal Article (14 results)

  • [Journal Article] NARF, an nemo-like kinase-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor.2006

    • Author(s)
      Yamada, M., Ohnishi.J., et al.
    • Journal Title

      J. Biol. Chem. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] NARF, an nemo-like kinase-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor.2006

    • Author(s)
      Yamada, M., Ohnishi, J., et al.
    • Journal Title

      J.Biol.Chem. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functions for proteinases in the ovulatory process.2005

    • Author(s)
      Ohnishi, J., et al.
    • Journal Title

      Biochim. Biophys. Acta 1745

      Pages: 95-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential roles of rennin and angiotensinogen in the feto-maternal interface to the development of complications of pregnancy.2005

    • Author(s)
      Takimoto-Ohnishi, E., et al.
    • Journal Title

      Mol. Endocrinol. 19

      Pages: 1361-1372

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functions for proteinases in the ovulatory process.2005

    • Author(s)
      Ohnishi, J., et al.
    • Journal Title

      Biochim.Biophys.Acta 1745

      Pages: 95-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential roles of rennin and angiotensinogen in the feto-maternal interface to the development of complications of pregnancy.2005

    • Author(s)
      Takimoto-Ohnishi, E., et al.
    • Journal Title

      Mol.Endocrinol. 19

      Pages: 1361-1372

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functions for proteinases in the ovulatory process2005

    • Author(s)
      Junji Ohnishi
    • Journal Title

      Biochemica et Biophysica Acta 1751

      Pages: 95-109

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Differential roles of rennin and angiotensinogen in the feto-maternal interface in the development of complications of pregnancy2005

    • Author(s)
      Eriko Takimoto-Ohnishi
    • Journal Title

      Molecular Endocrinology 19

      Pages: 1361-1372

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Proteases roles in ovulation.2005

    • Author(s)
      Ohnishi J. et al.
    • Journal Title

      Biochim.Biophys.Acta (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The possible involvement of matrix metalloproteinase-23(MMP-23) activity in ovulatory processes and conditioned switching of its expression during follicular development.2004

    • Author(s)
      Ohnishi, J., et al.
    • Journal Title

      Biol. Reprod. Special Issue

      Pages: 224-224

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Occurrence of a serine protease that could trigger the operation of the plasminogen activator/plasmin system in follicles of human ovaries.2004

    • Author(s)
      Ohnishi, J., et al.
    • Journal Title

      Mol. Reprod. Dev. 67

      Pages: 178-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The possible involvement of matrix metalloproteinase-23 (MMP-23) activity in ovulatory processes and conditioned switching of its expression during follicular development.2004

    • Author(s)
      Ohnishi, J., et al.
    • Journal Title

      Biol.Reprod.Sp.Iss. 224

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Occurrence of a serine protease that could trigger the operation of the plasminogen activator/plasmin system in follicles of human ovaries.2004

    • Author(s)
      Ohnishi, J., et al.
    • Journal Title

      Mol.Reprod.Dev. 67

      Pages: 178-185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Occurrence of a serine protease that could trigger the operation of the plasminogen activator/plasmin system in follicles of human ovaries.2004

    • Author(s)
      Ohnishi J. et al.
    • Journal Title

      Mol.Reprod.Dev. 67

      Pages: 178-178

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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