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Functional analysis of connective tissue factors involved in the epithlial remodeling of the digestive tract

Research Project

Project/Area Number 14570025
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionNippon Medical School (2004)
Dokkyo Medical University (2002-2003)

Principal Investigator

OKA Atuko  Nippon Medical School, Department of Biology, Professor, 医学部, 教授 (50175254)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsdigestive tract / organ remodeling / thyroid hormone / tissue interaction / apoptosis / stem cell / organ culture / electroporation / MMP / 甲状腺ホルモン応答遺伝子 / 電子顕微鏡 / 遺伝子導入 / 再生 / bZip / 骨形成蛋白質
Research Abstract

In the digestive tract during amphibian metamorphosis, under the control of the connective tissue, the larval epithelium undergoes apoptosis, whereas a small number of stem cells actively proliferate and form the adult epithelium similar to the mammalian counterpart. We previously examined expression profiles of thyroid hormone(TH) response genes and found that the connective tissue-specific expression of stromelysis-3 (ST3;MMP11) correlates well with the epithelial apoptosis, whereas that of BMP-4 correlates with development of the adult epithelium in the Xenopus laevis intestine. In this study, to clarify molecular mechanisms of the intestinal remodeling, we focused on functions of these TH response genes. First, using transgenic tadpoles expressing ST3 under the control of a heat shock-inducible promoter, we have shown by electron microscopy that the overexpression of ST3 induces apoptosis of the intestinal epithelium possibly through the modification of its basal lamina. Next, we performed organ culture experiments with BMP-4 and its antagonist, Chordin, proteins and have shown that BMP-4 causes precocious differentiation of the adult intestinal epithelium and inhibits cell proliferation of the connective tissue. Finally, to analyze functions of TH response genes more precisely, we established an in vitro gene transfer system by combining electroporation with organ culture techniques. Using this system, we overexpressed one of TH response genes, TH/bZip, in the epithelium of Xenopus tadpole intestines and demonstrated that TH/bZip functions as a growth activator during the intestinal remodeling. This in vitro system may provide a powerful tool for clarifying molecular mechanisms underlying the intestinal remodeling.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 2003 2002 Other

All Journal Article (9 results) Book (6 results) Publications (5 results)

  • [Journal Article] Epithelial-connective tissue cross-talk is essential for regeneration of intestinal epithelium2005

    • Author(s)
      Ishizuya-Oka, A.
    • Journal Title

      J.Nippon Med.Sch. 72

      Pages: 13-18

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epithelial-connective tissue cross-talk is essential for regeneration of intestinal epithelium.2005

    • Author(s)
      Ishizuya-Oka, A.
    • Journal Title

      J.Nippon Med.Sch. 72

      Pages: 13-18

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epithelial-connetive tissue cross-talk is essential for regeneration of intestinal epithelium2005

    • Author(s)
      Ishizuka-Oka, A
    • Journal Title

      Journal of Nippon Medical School 72(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Spatial and temporal expression pattern of a novel gene in the frog Xenopus laevis : correlations with adult intestinal epithelial differentiation during metamorphosis.2004

    • Author(s)
      Buchholz, D.R., Ishizuya-Oka, A., Shi, Y.-B.
    • Journal Title

      Gene Expression Patterns 4

      Pages: 321-328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spatial and temporal expression pattern of a novel gene in the frog Xenopus laevis : correlations with adult intestinal epithelial differentiation during metamorphosis.2004

    • Author(s)
      Buchholz, D.R., Ishizuya-Oka, A., Shi, Y.-B
    • Journal Title

      Gene Expression Patterns 4

      Pages: 321-328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spatial and temporal expression pattern of a novel gene in the frog Xenopus laevis: correlations with adult intestinal epithelial differentiation during metamorphosis.2004

    • Author(s)
      Buchholz, D.R., Ishizuka-Oka, A., Shi, Y.-B.
    • Journal Title

      Gene Expression Patterns 4

      Pages: 321-328

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thyroid hormone-up-regulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling.2003

    • Author(s)
      Ishizuya-Oka, A., Shimizu, K., Sakakibara, S., Okano, H., Ueda, S.
    • Journal Title

      J.Cell Science 116

      Pages: 3157-3164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Isolation of connective tissue-specific genes involved in Xenopus intestinal remodeling : thyroid hormone up-regulates Tolloid/BMP-1 expression.2002

    • Author(s)
      Shimizu, K., Ishizuya-Oka, A., Amano, T., Yoshizato, K., Ueda, S.
    • Journal Title

      Dev.Genes Evol. 212

      Pages: 357-364

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Isolation of connective tissue-specific genes involved in Xenopus intestinal remodeling : thyroid hormone up-regulates Tolloid/BMP-1 expression.2002

    • Author(s)
      Shimizu, K., Ishizuya-Oka, A., Amano, T., Yoshizato, K., Ueda S.
    • Journal Title

      Dev.Genes Evol. 212

      Pages: 357-364

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Regulation of apoptosis by extracellular matrix during postembryonic development in Xenopus laevis. In : When cells die? : a comprehensive evaluation of apoptosis and programmed cell death. (Eds. Lockshin, R.A., Zakeri, Z.)2004

    • Author(s)
      Ishizuya-Oka, A., Amano, T., Fu, L., Shi, Y.-B.
    • Publisher
      John Wiley & Sons
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Regulation of apoptosis by extracellular matrix during postembryonic development m Xenopus laevis. In When Cells Die? : a comprehensive evaluation of apoptosis and programmed cell death. (Eds.Lockshin, R.A., Zakeri, Z.)2004

    • Author(s)
      Ishizuya-Oka, A., Amano, T., Fu, Land Shi, Y.-B.
    • Publisher
      John Wiley & Sons, New Jersey
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 「人体発生学」第11章 呼吸器系、第12章消化器系(遠山正邇他編)2003

    • Author(s)
      岡 敦子(分担)
    • Publisher
      南山堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Thyroid hormone-induced apoptosis during amphibian metamorphosis. In : Molecular mechanisms of programmed cell death. (Eds. Shi, Y. et al.)2003

    • Author(s)
      Amano, T., Fu, L., Ishizuya-Oka, A., Shi, Y.-B.
    • Publisher
      Kluwer Academic/Plenum
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Thyroid hormone-induced apoptosis during amphibian metamorphosis. In Molecular Mechanisms of Programmed Cell Death. (Eds.Shi, Y. et al.)2003

    • Author(s)
      Amano, T., Fu, L., Ishizuya-Oka, A., Shi, Y.-B.
    • Publisher
      Kluwer Academic/Plenum, New York
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 「大腸癌」第III章発生と解剖1.組織発生(武藤徹一郎監修)2002

    • Author(s)
      岡 敦子(分担)
    • Publisher
      日本メディカルセンター
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ishizuya-Oka, A., Shimizu, K., Sakakibara, S., Okano, H., Ueda, S.: "Thyroid hormone-up-regulated expression of Musasbi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling."J.Cell Science. 116. 3157-3164 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Amano, T., Fu, L., Ishizuya-Oka, A., Shi, Y.-B.: "Thyroid hormone-induced apoptosis during amphibian metamorphosis. In : Molecular mechanisms of programmed cell death. (Eds. Shi, Y, Cidlowski, J.A., Scott, D., Wu, J., Shi, Y-B.)"Kluwer Academic/Plenum. 9-19 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishizuya-Oka, A., Amano, T., Fu, L., Shi, Y.-B.: "Regulation of apoptosis by extracellular matrix during postembryonic development in Xenopus laevis. In : When cells die? II : A comprehensive evaluation of apoptpsos and programmed cell death. (Eds. Lockshin, R.A., Zakeri, Z.)"John Wiley & Sons. 123-141 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu, K., Ishizuya-Oka, A., Amano, T., Yoshizato, K., Ueda, S.: "Isolation of connective tissue-specific genes involved in Xenopus intestinal remodeling : thyroid hormone up-regulates Tolloid/BMP-1 expression"Dev. Gene Evol.. 212. 357-364 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 岡 敦子: "武藤徹一郎監修「大腸癌」第III章発生と解剖1. 組織発生"日本メディカルセンター. 72-75 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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