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Molecular cloning and functional analysis of genes associated with mucosal defense to investigate patbophysiology of inflammatory bowel disease

Research Project

Project/Area Number 13470249
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTohoku University

Principal Investigator

FUKUSHIMA Kouhei  Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (20271900)

Co-Investigator(Kenkyū-buntansha) FUNAYAMA Yuji  Tohoku University, Hospital, Lecturer, 医学部附属病院, 講師 (50192315)
SASAKI Iwao  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60125557)
内藤 広郎  東北大学, 医学部・附属病院, 講師 (90180223)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 2003: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2001: ¥7,100,000 (Direct Cost: ¥7,100,000)
Keywordsintestinal flora / inflammatory bowel disease / microarray / epithelial cells / Germ-free / ulcerative colitis / Crohn's disease / resistin-like molecule / FIZZ / クローニング
Research Abstract

We identified resistin-like molecule β (RELM-β) and deleted malignant brain tumors 1(DMBT1) as molecules induced by bacterial challenge to germ-free mice and associated with mucosal defense against enteric flora. We investigated expression of those genes and proteins in mucosal tissues of experimental and human inflammatory bowel disease and induction mechanisms of the molecules.
Antibacterial activity of RELM-β
RELM-β was selectively expressed in the colon and secreted from epithelial cells into the lumen. Immunoreactive RELM-β was present in stool, suggesting possible interaction of the protein with enteric flora. We investigated whether or not RELM-β is capable of inhibiting bacterial growth against panels of enteric flora by CFU assay, resulting that this protein exhibited anti-bacterial capacity against Staphylococcus aureus.
Epithelial induction of a human homologue of murine CRP-ductin, Deleted in Malignant Brain Tumors 1 (DMBT1)
Induction of CRP-ductin mRNA was initially detected by cDNA microarray. This gene was also induced in DSS-colitis even after recovery from active inflammation by the removal of DSS. Northern blotting revealed that the human homologue, DMBT1 with 7 kb in size, was weakly expressed in control but remarkably induced in two-thirds of IBD isolates. An additional 6.5 kb band was noticed in one-third of IBD isolates. Real-time RT-PCR demonstrated that DMBT1 mRNA level was significantly higher in both DC and CD. However, qualitative difference in DMBT1 protein expression was not identified by immunohistochemistry. This gene was induced by soluble factors including IL-1β.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Fukushima K, et al.: "Epithelial induction of serum amyloid A in experimental mucosal inflkammation."Digestive Diseases and Sciences. 47. 1438-1446 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa H, et al.: "Increased Expression of HIP/PAP and Regenerating Gene III in Human Inflammatory Bowel Disease and a Murine Bacterial Reconstitution Model."Inflammatory Bowel Diseases. 9(3). 162-170 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Decreased expression of syncollin mRNA in colonic epithelial cells of bacteria-challenged germ-free mice and ulcerative colitis."Digestive Diseases and Sciences. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Inflammatory bowel disease-associated gene expression in intestinal epithelial cells by differential cDNA screening and mRNA display."Inflammatory Bowel Diseases. 9(5). 290-301 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis."Am J Physiol Gastrointestinal Liver Physiol. 286. G804-G813 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Epithelial induction of serum amyloid A in experimental mucosal inflkammation."Digestive Diseases and Sciences. 47. 1438-1446 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa H, et al.: "Increased Expression of HIP/PAP and Regenerating Gene III in Human Inflammatory Bowel Disease and a Murine Bacterial Reconstitution Model."Inflammatory Bowel Diseases. 9(3). 162-170 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Decreased expression of syncollin mRNA in colonic epithelial cells of bacteria-challenged germ-free mice and ulcerative colitis."Digestive Diseases and Sciences. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Inflammatory bowel disease-associated gene expression in intestinal epithelial cells by differential cDNA screening and mRNA display."Inflammatory Bowel Diseases. 9(5). 290-301 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima K, et al.: "Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis."Am J Physiol Gastrointestinal Liver Physiol. 286. G804-G813 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Fukushima ほか: "Non-pathogenic bacteria modulate colonic epithelial gene expression in germ-free mice"Scand J Gestroenterol. 38. 626-634 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 福島浩平 ほか: "消化管(IV)炎症性腸疾患"臨床透析. 19. 934-939 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K Fukushima ほか: "Inflammatory Bowel Disease-associated gene expression in intestinal epithelial cells by differential cDNA screening and mRNA display"Inflammatory Bowel Disease. 9. 290-301 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H Ogawa, K FUkushima ほか: "Increased expression of HIP/PAP and regenerating gene III in human inflammatory bowel disease and a murine bacterial reconstitution model"Inflammatory Bowel Disease. 9. 162-170 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K Fukushima ほか: "Paradoxical decrease of mitochondrial DNA deletion in epithelial cell of active ulcerative colitis patients"Am J Physiol(Gastrointestinal Liver Physiol). (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 福島浩平: "Inflammatory Bowel Disease-associated gene expression in intestinal epithelial cells by differential cDNA screening and mRNA display"Inflammatory Bowel Disease. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小川 仁: "Increased expression of HIP/PAP and Reg III in human and experimental bowel disease"Inflammatory Bowel Disease. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 福島浩平: "Non-pathogenic bacteria modulates colonic epithelial gene expression in germ-free mice"Scand. J. Gastroenterology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Fukushima et al.: "Epithelial induction of serum amyloid A in expenmental mucosal inflammation"Digestive Diseases and Sciences. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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