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

Identification of the Notch signal in intestinal epithelial cells and the failure of the intestinal differentiation in chronic colitis.

Research Project

Project/Area Number 17590624
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OKADA Eriko  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Fellow, 医学部附属病院, 医員 (20376784)

Co-Investigator(Kenkyū-buntansha) KUBOTA Daisuke  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Fellow, 医学部附属病院, 医員 (00376790)
TSUCHIYA Kiichiro  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 大学院医歯学総合研究科, 助手 (40376786)
WATANABE Mamoru  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Professor (10175127)
大島 茂  東京医科歯科大学, 医学部附属病院, 医員 (50376787)
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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsNotch / Chronic colitis / Regeneration / Stem Cell / Notchシグナル / 腸管分化 / 転写因子
Research Abstract

In this study, we demonstrated that Notch signaling plays a crucial role in the differentiation of intestinal epithelial cells, and then we revealed several genes directly targeted by Notch signal in intestinal epithelial cells.
It has been reported that the deficient of HES1 gene via Notch signaling caused the differentiation of intestinal epithelial cells, indicating that Notch signaling regulates the dedifferentiation of intestinal epithelial cells. However the function of Notch signaling has been unknown. Therefore, we aimed to elucidate the effect of Notch signaling in intestinal epithelial cells. First, we established the system of Notch signal stimulation, using the expression of Notch intracellular domain (NICD) induced by doxycycline. Moreover, we established the system of Notch signal inhibition, using γ-secretase inhibitor that suppresses the separation of NICD. The expression of NICD caused the dedifferentiation of intestinal epithelial cells such as the decrease of Mucin2 gene and Hath1 gene, on the contrary, the inhibition of Notch signal caused the differentiation with the increase of Mucin2 gene and Hath1 gene. Therefore, we identified several genes directly targeted by Notch signal stimulation, using RNA micro array analysis for the clarification of Notch function in intestine.
Because Notch signal regulates the differentiation of intestinal cell line, we examined the expression of NICD in human intestine and human colitis. NICD was expressed at the lower crypt, whereas Hes1 and Ki-67 were expressed. Moreover, in intestine of IBD patient, NICD was expressed at higher crypt than in normal intestine, suggesting that the increase of Notch signal suppress the differentiation of the intestinal epithelial cells in IBD. So we assessed the effect of γ-secretase inhibitor on intestinal epithelial cells. The inhibition of Notch signal caused the increase of goblet cells in mouse, indicating that Notch signal may be new target for the therapy of IBD.

Report

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

    (11 results)

All 2007 2006 2005 Other

All Journal Article (10 results) Book (1 results)

  • [Journal Article] IL-7 is essential for the development and the persistence of chronic colitis.2007

    • Author(s)
      Totsuka T, Tsuchiya K, Watanabe M, et al.
    • Journal Title

      J Immunol. 178

      Pages: 4737-4748

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intestinal lamina propria retaining CD4+CD25+ regulatory T cells is a suppressive site of intestinal inflammation.2007

    • Author(s)
      Makita S, Tsuchiya K, Watanabe M, et al.
    • Journal Title

      J Immunol. 178

      Pages: 4937-4946

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reciprocal targeting of Hath1 and β-catenin by Wnt-glycogen synthase kinase 3β in human colon cancer.2007

    • Author(s)
      Tsuchiya K, Watanabe M, et al.
    • Journal Title

      Gastroenterology. 132

      Pages: 208-220

    • NAID

      40015644487

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] FTY720 suppresses CD4^+CD44^<high>CD62L^- effector memory T cell-mediated colitis.2006

    • Author(s)
      Fujii R, Tsuchiya K, Watanabe M, et al.
    • Journal Title

      Am J Physiol. 291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 新しい工夫・ダブルオーバーチューブ法によるダブルバルーン内視鏡の報告2006

    • Author(s)
      荒木昭博, 岡田英理子, 他
    • Journal Title

      Progress of Digestive Endoscopy. 68・2

      Pages: 53-57

    • NAID

      130004985191

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] FTY720 suppresses CD4^+CD44^<high>CD62L^- effector memory T cell-mediated colitis2006

    • Author(s)
      Fujii R, Tsuchiya K, Watanabe M, et al.
    • Journal Title

      Am J Physiol. 291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IRF-1 mediates upregulation of LMP7 by IFN-gamma and concerted expression of immunosubunits of the proteasome.2005

    • Author(s)
      Namiki S, Tsuchiya K, Watanabe M, et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 2781-2787

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IL-7 exacerbates chronic colitis with expansion of memory IL-7Rhigh CD4+ mucosal T cells in mice.2005

    • Author(s)
      Okada E, Watanabe M, et al.
    • Journal Title

      Am J Physiol. 288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.2005

    • Author(s)
      Matsumoto T, Tsuchiya K, Watanabe M, et al.
    • Journal Title

      Gastroenterology. 128

      Pages: 1851-1867

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.

    • Author(s)
      Matsumoto T, Tsuchiya K, Watanabe M, et al.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 消化器疾患の最新治療2005-20062006

    • Author(s)
      岡田英理子, 渡辺 守
    • Total Pages
      476
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi