• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of the epigenetic treatment against inflammatory bowel disease with targeting chromatin remodeling

Research Project

Project/Area Number 17590661
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

ARIMURA Yoshiaki  Sapporo Medical University, Medicine, Assistant professor, 医学部, 講師 (80305218)

Co-Investigator(Kenkyū-buntansha) GOTO Akira  Sapporo Medical University, Medicine, Instructor, 医学部, 助手 (40381272)
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: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsDNA methylation inhibitor / HDAC inhibitor / epigenetics / mouse experimental colitis
Research Abstract

1.Examination of therapeutic effect in the mouse experimental colitis
A single or combination administration of DNA methylation inhibitor (Aza-dC) and histone deacetylase (HDAC) inhibitor (FK228) was evaluated on therapeutic efficacy for the mouse DSS colitis.
Colitis was induced by 3% DSS for four days ad libitum in Balb/c mouse.
We divided it into our groups : DNA methylation inhibitor (Aza-dC) single administration group, HDAC inhibitor (FK228) single administration group, combined administration group, and control group and we explored the preventive and therapeutic effect of treatment.
As a result, colitis rather accepted a tendency to worsen in an Aza-dC single administration group, while colitis was ameliorated in the combination group, which did not reach a statistically significant difference comparing with the control group, but preventive and therapeutic effect of treatment in FK228 group was proven.
We next examined mouse TNBS colitis, where significant preventive and therapeutic effect of treatment in FK228 group was only demonstrated in DSS colitis.
2.The in vivo analysis of the anti-inflammatory action mechanism of HDAC inhibitor
We reviewed various cytokine profiles using colonic tissue in the mouse TNBS colitis by ELISA.
As a result, TNFα, IFN-γ, and IL-6 expression was decreased in a dose-dependent manner, but a significant difference was not found in IL-10 expression level.
Furthermore, we isolated lamina propria lymphocytes (LPMC) from DSS colitis, and acetylation of H3 was detected in a FK228 dose-dependent manner revealed by Western blotting using an anti acetyl-histone (H3) antibody.
3.Examination of the epigenetic abnormality in the experimental colitis
We genome-widely analyze gene expression changes with the chemical administration by cDNA array, and candidate genes whose silencing is canceled and expressing are going to be checked the chromatin remodeling state of the promoter region of those in future.

Report

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

    (4 results)

All 2006 2005

All Journal Article (4 results)

  • [Journal Article] Antisense therapy of MAdCAM-1 for trinitrobenzenesulfonic acid-induced murine colitis2006

    • Author(s)
      Goto A
    • Journal Title

      Inflamm Bowel Dis 12

      Pages: 758-765

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Therapeutic implications of the specific inhibition of causative matrix metalloproteinases in experimental colitis induced by dextran sulphate sodium2006

    • Author(s)
      Kobayashi K
    • Journal Title

      J Pathol 209

      Pages: 376-383

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Therapeutic implications of the specific inhibition of causative matrix metalloproteinases in experimental colitis induced by dextran sulphate sodium2006

    • Author(s)
      Kobayashi K
    • Journal Title

      J Pathol in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis2005

    • Author(s)
      Okahara S
    • Journal Title

      Aliment Pharmacol Ther 21

      Pages: 1091-1097

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi