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潰瘍性大腸炎およびColitic Cancer発症におけるREG蛋白の役割の解明

Research Project

Project/Area Number 15659169
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKyoto University

Principal Investigator

千葉 勉  京都大学, 医学研究科, 教授 (30188487)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsReg遺伝子 / REG蛋白 / 潰瘍性大腸炎 / 炎症性サイトカイン / Colitic cancer / アポトーシス / reg遺伝子 / H.pylori / 胃炎 / 胃癌 / colitic cancer
Research Abstract

1.潰瘍性大腸炎の持続炎症からcolitic cancerの発癌に至る過程におけるREG蛋白の役割を明らかにするために、前回のreg遺伝子発現の検討をLoVo細胞を用いてさらにすすめた。その結果regIα遺伝子プロモーターのプロモーターアッセイでは、やはりIFN-γとIL-6のみが増強作用を有しており、特にIL4,IL5,IL13などのTh2系サイトカインにはreg遺伝子発現増強作用はまったく認められなかった。
2.さらにREG蛋白は前回の検討で、細胞増殖作用ならびに抗アポトーシス作用を有することが判明したが、今回の検討でreg蛋白はAktのリン酸化を介して、BclXL,Bcl2蛋白の発現を増強させることが明らかとなった。さらにこれらの作用はREG蛋白発現細胞株で認められること、またその作用が抗REG抗体で消失することから、REG蛋白はautocrine機序で、これらの作用を発揮していると考えられた。
3.一方REG蛋白の発現は、ヒトでは潰瘍性大腸炎のみならず、クローン病、Proctitisにおいても、強く認められた。なおその際特に潰瘍性大腸炎では、reg遺伝子の発現は、炎症の程度、さらに病悩期間と強い相関を認めた。したがってreg遺伝子、REG蛋白の発現は、胃におけるのと同様、様々な炎症において広く発現していることが明らかとなった。
4.以上のように、REG蛋白は潰瘍性大腸炎においてその発現が増強しており、colitic cancerの発症に重要な役割を果たしていると考えられるが、この現象は潰瘍性大腸炎に特徴的なTh2反応を介しているのではなく、主としてIFN-γやIL-6など、より一般的な炎症性サイトカインの発現によってもたらされることが明らかとなった。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2005 2004 Other

All Journal Article (6 results) Publications (11 results)

  • [Journal Article] Hes1-deficient mice show precocious differentiation of Paneth cells in the small intestine.2005

    • Author(s)
      Suzuki K, Chiba T, et al.
    • Journal Title

      Biochem Biophys Res Commun 328(1)

      Pages: 348-352

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Successful treatment for doudeno-colonic fistula in a patient with Crohn's disease with tacrolims.2005

    • Author(s)
      Fukuda A, Chiba T, et al.
    • Journal Title

      J Gastroenterol (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis.2005

    • Author(s)
      Matsuura M, Chiba T, et al.
    • Journal Title

      Gastroenterology (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of colonic neoplasia in p53 deficient mice with experimental colitis induced by dextran sulfate sodium.2004

    • Author(s)
      Fujii S, Chiba T, et al.
    • Journal Title

      Gut 53(5)

      Pages: 710-716

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nuclear b-Catenin Accumulation as a Prognostic Factor in Dukes' D Human Colorectal Cancers.2004

    • Author(s)
      Miyamoto S, Chiba T, et al.
    • Journal Title

      Oncol Rep 12(2)

      Pages: 245-251

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reg protein is a unique growth factor of gastric mucosal cells.2004

    • Author(s)
      Kinoshita Y, Chiba T, et al.
    • Journal Title

      J Gastroenterol 39(6)

      Pages: 507-513

    • NAID

      10013296093

    • Related Report
      2004 Annual Research Report
  • [Publications] Kanai M, Chiba T, et al.: "Differentiation inducing factor-i (DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK- ERK-dependent pathway."Oncogene. 22. 548-554 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takaishi S, Chiba T, et al.: "The growth promoting effect of thioredoxin on intestinal epithelial cells."Dig Dis Sci. 48. 379-385 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kayahara T, Chiba T, et al.: "Candidate markers for stem and early progenitor cells, Musashi-1 and Hesl, are expressed in crypt base columnnar cells of mouse small intestine."FEBS Lett. 535. 131-135 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii S., Fujimori T., Chiba T: "Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia."J Exp Clin Cancer Res J Exp Clin Cancer Res. 22. 421-429 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukui H., Chiba T., et al.: "Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in mongolian gerbils."Lab Invest. 83. 1777-1786 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyaoka Y, Chiba T, et al.: "Transgenic overexpression of Reg protein caused gastric cell proliferation and differentiation along parietal cell and chief cell lineages."Oncogene. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii S, Chiba T, et al.: "Development of colonic neoplasia in p53 deficient mice with experimental colitis induced by dextran sulfate sodium."Gut. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii S, Chiba T, et al.: "Efficacy of surveillance and molecular markers for detection of ulcerative colitis-associated colorectal neoplasia."J Gastroenterol. 38. 1117-1125 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukui H, Chiba T, et al.: "Expression of RegIα protein in human gastric cancer."Digestion. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanda N, Chiba T, et al.: "STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells."Oncogene. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chiba T, Kinoshita Y, et al.: "Reg protein : A mediator of gastrin-induced gastric mucosal proliferation."Gastrin. (in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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