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Novel function "regulation of extracellular matrix construction" of ectopic AID expression in wound healing process.

Research Project

Project/Area Number 20K08318
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKurume University

Principal Investigator

Okada Toshiyuki  久留米大学, 医学部, 助教 (10607328)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords炎症性腸疾患 / AID / 異所性発現 / AICDA / DSS / 大腸上皮細胞 / 上皮再生 / 細胞外マトリックス / 大腸炎
Outline of Research at the Start

難治性の慢性炎症疾患である潰瘍性大腸炎とクローン病患者の寛解状態を長く維持するためには『粘膜治癒させることが重要』であるが、粘膜の創傷治癒過程に関する理解が不十分である。近年では、基底膜側に存在する間質細胞が腸管上皮幹細胞の恒常性維持と上皮構造のリモデリングに重要な事が報告された 。そこで本研究では、炎症条件下に大腸上皮細胞で異所性発現するActivation-Induced cytidine Deaminase (AID)が、ECM関連分子の発現調節を介して、損傷した大腸粘膜の創傷治癒に重要な間質細胞の種類(バランス)を変化させている可能性について検討を行う。

Outline of Final Research Achievements

To evaluate the role of AID, which is ectopically expressed in colonic epithelial cells (CECs) under inflammatory conditions, wild-type (WT) and AID-deficient mice were evaluated using the DSS-induced colitis model. Restoration of body weight loss after colitis induction is delayed in AID-deficient mice compared to WT mice. In addition, the expression of extracellular matrix-associated molecules in CECs of WT and AID-deficient mice transitioned to the recovery phase was not only significantly altered, but also the disease score of colon tissue was significantly higher in AID-deficient mice compared to WT mice. Additionally, we found that AID, which is ectopically expressed under inflammation conditions, binds to target genes and induces DNA demethylation, possibly regulating the expression of those genes using colorectal cancer cell lines stably expressing AID.

Academic Significance and Societal Importance of the Research Achievements

本研究成果より、炎症に伴って大腸上皮細胞に異所性発現するAIDの役割を理解することは、大腸粘膜を治癒(創傷治癒過程)させるためのメカニズムを理解するための一助になることが期待できると考えられる。さらに先行研究では異所性なAIDの発現は、上皮細胞の悪性転換に関与する可能性が報告がされていることからも、慢性炎症による発がん機構の解明にも貢献できる可能性が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020 Other

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Chitinase 3-like 1, Carcinoembryonic Antigen-related Cell Adhesion Molecule 6, and Ectopic Claudin-2 in the Carcinogenic Processes of Ulcerative Colitis2022

    • Author(s)
      KINUGASA TETSUSHI、TSUNODA TOSHIYUKI、MIZOGUCHI EMIKO、OKADA TOSHIYUKI、SUDO TOMOYA、KAWAHARA AKIHIKO、AKIBA JUN、AKAGI YOSHITO
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 8 Pages: 4119-4127

    • DOI

      10.21873/anticanres.15910

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Landscape of inflammatory bowel disease in Singapore2022

    • Author(s)
      Low Daren、Swarup Nidhi、Okada Toshiyuki、Mizoguchi Emiko
    • Journal Title

      Intestinal Research

      Volume: 2021.00089. Issue: 3 Pages: 00089-00089

    • DOI

      10.5217/ir.2021.00089

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological Analyses-Derived Translational Findings in the T Cell Receptor Alpha Chain Knockout Mouse as an Experimental Model for Ulcerative Colitis2021

    • Author(s)
      Mizoguchi Emiko、Sadanaga Takayuki、Okada Toshiyuki
    • Journal Title

      International Journal of Translational Medicine

      Volume: 1 Issue: 3 Pages: 187-204

    • DOI

      10.3390/ijtm1030014

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Review of Selected IBD Biomarkers: From Animal Models to Bedside2021

    • Author(s)
      Emiko Mizoguchi, Renuka Subramaniam, Toshiyuki Okada, and Atsushi Mizoguchi
    • Journal Title

      Diagnostics

      Volume: 11 Issue: 2 Pages: 207-207

    • DOI

      10.3390/diagnostics11020207

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recent updates on the basic mechanisms and pathogenesis of inflammatory bowel diseases in experimental animal models2020

    • Author(s)
      Emiko Mizoguchi, Daren Low, Yui Ezaki, and Toshiyuki Okada
    • Journal Title

      Intestinal Research

      Volume: 18 Issue: 2 Pages: 151-167

    • DOI

      10.5217/ir.2019.09154

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Themis in peripheral CD8 T cells regulates hapten-induced allergic skin inflammation2022

    • Author(s)
      Masayuki Kitajima, Toshiyuki Okada, Harumi Suzuki.
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Role of a putative cyclin-binding domain in one of the nuclear localization sequences of Chitinase 3-like 1 in colonic epithelial cells2021

    • Author(s)
      Emiko Mizoguchi, Toshiyuki Okada, Takanori Minagawa, Chun-Geun Lee, Jack A. Elia, Atsushi Mizoguchi.
    • Organizer
      日本免疫学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 口腔扁平上皮発癌におけるChitinase 3-like 1 の関与2020

    • Author(s)
      寺谷由唯、楠川仁悟、岡田季之、溝口充志、溝口恵美子
    • Organizer
      第57回日本消化器免疫学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 大腸炎によって異所性発現するAIDの役割2020

    • Author(s)
      岡田季之、溝口充志、溝口恵美子、齋藤成昭
    • Organizer
      第57回日本消化器免疫学会総会
    • Related Report
      2020 Research-status Report
  • [Book] 消化器病学サイエンス 5(2) 初心者でもわかるゲノム編集技術2021

    • Author(s)
      岡田季之、 皆川貴範、溝口恵美子
    • Publisher
      先端医学社
    • Related Report
      2021 Research-status Report
  • [Remarks] エピゲノム免疫学

    • URL

      http://www.med.kurume-u.ac.jp/med/immun/okada.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] エピゲノム免疫学

    • URL

      http://www.med.kurume-u.ac.jp/med/immun/

    • Related Report
      2021 Research-status Report
  • [Remarks] 久留米大学 医学部医学科 免疫学

    • URL

      http://www.med.kurume-u.ac.jp/med/immun/

    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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