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Functional analysis of glycodelin induced by HDACI in endometrial glandular epithelium.

Research Project

Project/Area Number 16591683
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

UCHIDA Hiroshi  Keio University, School of Medicine, Instructor, 医学部, 助手 (90286534)

Co-Investigator(Kenkyū-buntansha) MARUYAMA Tetsuo  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (10209702)
YOSHIMURA Yasunori  Keio University, School of Medicine, Professor, 医学部, 教授 (10129736)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordshuman endometrium / histone deacetylase inhibitor / differentiation / migration / glycodelin / 細胞浸潤 / glycodelin
Research Abstract

Human uterine endometrium repeats proliferation, differentiation (decidualization) and tissue breakdown during the menstrual period. Histone reversible acetylation, regulated by histone acetylase and deacetylase, govern gene transcription. To develop new strategy of treatment for impairment of implantation, we analyze the possibility of histone deacetylase inhibitors (HDACI) as a differentiation inducer of human endometrium, instead of ovarian steroid hormones.
We analyzed the effect of ovarian steroid hormones or HDACI onto Ishikawa cells (human adenocarcinoma cell line), which is used as a model of human endometrial glandular epithelium. In a similar way to ovarian steroid hormones, HDACI affected the following function in Ishikawa cells.
1)HDACI induced the both mRNA and protein expression of glycodelin, which is highly expressed in differentiated (luteal-phase) endometrial gland, via glycodelin promoter region.
2)Flattened and wide-spread morphological changes of cells were shown by HDACI.
3)HDACI enhanced the production of glycogen.
4)HDACI up-regulated single cell motility, analyzed with trans-well cell migration assay.
5)HDACI enhanced collective cell motility, tested with wound healing assay.
6)Glycodelin permanent expression clones showed accelerated single and collective cell migration.
7)Glycodelin gene silencing by siRNA abolished the effect by HDACI, mentioned above.
Taken together, HDACI have a potential to induce both differentiation and migration of endometrial cells through up-regulation of glycodelin, providing a clue for a possible therapeutic strategy to modulate endometrial function by targeting glycodelin.

Report

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

    (10 results)

All 2006 2005 2004

All Journal Article (10 results)

  • [Journal Article] Human endometrial cytodifferentiation by histone deacetylase inhibitors.2006

    • Author(s)
      Uchida, Hiroshi
    • Journal Title

      Human Cell 19

      Pages: 38-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Human endometrial cytodifferentiation by histone deacetylase inhibitors2006

    • Author(s)
      Uchida H, et al.
    • Journal Title

      Hum Cell 19

      Pages: 38-42

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histone Deacetylase Inhibitors Induce Differentiation of Human Endometrial Adenocarcinoma Cells through Up-regulation of Glycodelin.2005

    • Author(s)
      Uchida, Hiroshi
    • Journal Title

      Endocrinology 146(12)

      Pages: 5365-5373

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histone acetylation in reproductive organs : significance of histone deacetylase inhibitors in gene transcription.2005

    • Author(s)
      Uchida, Hiroshi
    • Journal Title

      Reproductive Medicine and Biology 4(2)

      Pages: 115-122

    • NAID

      10015654605

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histone Deacetylase Inhibitors Induce Differentiation of Human Endometrial Adenocarcinoma Cells through Up-regulation of Glycodelin2005

    • Author(s)
      Uchida H, et al.
    • Journal Title

      Endocrinology 146(12)

      Pages: 5365-5373

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histone acetylation in reproductive organs : Significance of histone deacetylase inhibitors in gene transcription2005

    • Author(s)
      Uchida H, et al.
    • Journal Title

      Reprod Med Biol 4

      Pages: 115-122

    • NAID

      10015654605

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Histone Deacetylase Inhibitors Induce Differentiation of Human Endometrial Adenocarcinoma Cells through Up-regulation of Glycodelin2005

    • Author(s)
      Uchida, Hiroshi
    • Journal Title

      Endocrinology 146(12)

      Pages: 5365-5373

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Histone acetylation in reproductive organs : significance of histone deacetylase inhibitors in gene transcription2005

    • Author(s)
      Uchida, Hiroshi
    • Journal Title

      Reproductive Medicine and Biology 4(2)

      Pages: 115-122

    • NAID

      10015654605

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Histone acetylation in reproductive organs : significance of histone deacetylase inhibitors in gene transcription. (Review)2005

    • Author(s)
      Uchida H, Maruyama T, Arase T, Ono M, Nagashima T, Masuda H, Asada H, Yoshimura Y
    • Journal Title

      Reprod Med Biol 4(2)(In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Follicle stimulating hormone-secreting pituitary microadenoma with fluctuating levels of ovarian hyperstimulation.2004

    • Author(s)
      Maruyama T, Masuda H, Uchida H, Nagashima T, Yoshimura Y
    • Journal Title

      Obstet Gynecol. (In press)

    • Related Report
      2004 Annual Research Report

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

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