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Molecular biological study on the expression and functions of trefoil factor family(TFF) peptides in gastrointestinal mucosa

Research Project

Project/Area Number 15590679
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionDokkyo University School of Medicine

Principal Investigator

HIRAISHI Hideyuki (2004)  Dokkyo University, Department of Medicine, Professor, 医学部, 教授 (00199035)

寺野 彰 (2003)  獨協医科大学, 医学部, 教授 (50155470)

Co-Investigator(Kenkyū-buntansha) SHIMADA Tadahito  Dokkyo University, Department of Medicine, Associate Professor, 医学部, 助教授 (10206170)
TAMANO Masaya  Dokkyo University, Department of Medicine, Lecture, 医学部, 講師 (70265312)
YONEDA Masashi  Dokkyo University, Department of Medicine, Lecture, 医学部, 講師 (30261407)
FUJIMORI Takahiro  Dokkyo University, Department of Medicine, Professor, 医学部, 教授 (30095385)
平石 秀幸  獨協医科大学, 医学部, 助教授 (00199035)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordstrefoil factor family / stomach / colon / peptic ulcer / PPARγ / NSAIDs / サイトカイン
Research Abstract

Trefoil factor family(TFF) is a group of protease resistant peptides mainly expressed in gastrointestinal epithelial cells. To date, three TFF peptides are identified in humans, TFF1 (pS2), TFF2 (SP), and TFF3 (LTF). It is well established that TFF peptides play critical roles in the defense and repair of gastrointestinal mucosa. In this study, in order to understand the regulatory mechanisms of TFF expression, we examined the effects of growth factors, cytokines, ligands for various nuclear receptors, and NSAIDs on the expression of TFF in primazy cultured gastrointestinal mucosal cells as well as in cell lines derived from gastrointestinal epithelial cells. Endogenous TFF mRNA expression was analyzed by real-time quantitative RT-PCR and reporter gene assays were also performed. Major findings are as follows : (1)TFF1 was originally discovered as an estrogen-inducible gene in MCF-7 bieast cancer cells. Although we identified the expression of estrogen receptors(ER)(mainly ERβ) in gastric epithelial cells, 17β-estradiol had no significant effect on the expression of endogenous TFF1 mRNA as well as the transcription of TFF1 reporter genes, suggesting that gastric expression of TFF1 is independent of ER. (2)TNFα and phorbol ester up-regulated TFF1 expression. Reporter gene assay showed that NF-κB and AP-1 mediates the action of TNF-α and phorbol ester, respectively. (3)Ligands for PPARγ, such as troglitazone and 15d-PGJ2, were found to up-regulate TFF2 expression in gastric epithelial cells. We identified the presence of a functional peroxisome proliferator responsive element(PPRE) within the promoter region of human TFF2 gene. (4)We also found that NSAIDs, such as indomethacin and aspirin, up-regulates TFF2 expression through activating PPARγ. Since TFF2 is a critical cytoprotective agent, this mechanism may reduce the degree of gastric mucosal damage induced by these NSAIDs.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (44 results)

All 2005 2004 Other

All Journal Article (33 results) Publications (11 results)

  • [Journal Article] Effect of central corticotropin releasing factor on hepatic circulation in rats : the role of the CRF2 receptor in the brain2005

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Gut 54(2)

      Pages: 282-288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Protective effect of central thyrotropin-releasing hormoneanalog on cerulein-induced acute pancreatitis in rats2005

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Regul Rept 125(1-3)

      Pages: 119-124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Protective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatitis in rats.2005

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Regul Rept 125(1-3)

      Pages: 119-124

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of central corticotropin releasing factor on hepatic circulation in rats : the role of the CRF_2 receptor in the brain2005

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Gut 54(2)

      Pages: 282-288

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pratective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatis in rats2005

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Regul Rept 125(1-3)

      Pages: 119-124

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PPARγ mediates NSAIDs-induced upregulation of TFF2 expression in gastric epithelial cells.2004

    • Author(s)
      Shimada T et al.
    • Journal Title

      FEBS 558

      Pages: 33-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endoscopic Papillary Balloon Dilation for Treatment of Common Bile Duct Stones2004

    • Author(s)
      Watanabe H., Hiraishi H.et al.
    • Journal Title

      Hepatogastroenterology 51

      Pages: 652-657

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis2004

    • Author(s)
      Kanke K., Hiraishi H.et al.
    • Journal Title

      Dig Liver Dis 36(12)

      Pages: 811-817

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of quantitative neuropsy chological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese2004

    • Author(s)
      Kato A., Terano A.et al.
    • Journal Title

      Hepatol Res 30(2)

      Pages: 71-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transforming growth factor-β-induced stimulation of formation of collagen fiber network and anti-fibrotic effect of taurine in an in vitro model of hepatic fibrosis2004

    • Author(s)
      Kato J, Terano A. et al.
    • Journal Title

      Hepatol Res 30(1)

      Pages: 34-41

    • NAID

      10018025147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification and characterization of taxilin isoforms2004

    • Author(s)
      Nagami S, Terano A. et al.
    • Journal Title

      Biochem Biophys Res Common 319(3)

      Pages: 936-943

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intraportal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors2004

    • Author(s)
      Hashimoto T, Yoneda M. et al.
    • Journal Title

      Toxicol Apple Pharmacol 196(1)

      Pages: 1-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vitamin E Therapy in Patients With NASH2004

    • Author(s)
      Yoneda M et al.
    • Journal Title

      Hepatology 39(2)

      Pages: 568-568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 胃潰瘍診療ガイドラインにおけるGERDの考え方2004

    • Author(s)
      白川 勝朗 他
    • Journal Title

      日本臨床 62

      Pages: 1559-1564

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] PPARγ mediates NSAIDs-induced upregulation of TFF2 expression in gastric epithelial cells.2004

    • Author(s)
      Shimada T. et al.
    • Journal Title

      FEBS 558

      Pages: 33-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endoscopic Papillary Balloon Dilation for Treatment of Common Bile Duct Stones.2004

    • Author(s)
      Watanabe H. et al.
    • Journal Title

      Hepatogastroenterology 51

      Pages: 652-657

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis.2004

    • Author(s)
      Kanke K. et al.
    • Journal Title

      Dig Liver Dis. 36(12)

      Pages: 811-817

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of central corticotropin releasing factor on hepatic circulation in rats ; the role of the CRF2 receptor in the brain.2004

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Gut 54(2)

      Pages: 282-288

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of quantitative Neuropsy chological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter Collaborative study in Japanese.2004

    • Author(s)
      Kato A.et al.
    • Journal Title

      Hepatol Res 30(2)

      Pages: 71-78

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transforming growth factor-β-induced stimulation of formation of ollagen fiber network and anti-fibrotic effect of taurine in an vitro model of hepatic fibrosis.2004

    • Author(s)
      Kato J.et al.
    • Journal Title

      Hepatol Res. 30(1)

      Pages: 34-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification and characterization of taxilin isoforms.2004

    • Author(s)
      Nagami S
    • Journal Title

      Biochem Biophys Res Common 319(3)

      Pages: 936-943

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intrapartal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endotheline A and endothline B receptors.2004

    • Author(s)
      Hashimoto T. et al.
    • Journal Title

      Toxicol Apple Pharmacol 196(1)

      Pages: 1-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Vitamin E Therapy in patients with NASH.2004

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Hepatology 39(2)

      Pages: 568-568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recent view of gastro-Esophageal reflux disease according to the guideline for gastric ulcer treatment.2004

    • Author(s)
      Shirakawa K. et al.
    • Journal Title

      Nippon Rinsho 62(8)

      Pages: 1559-1564

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] PPARγ mediates NSAIDs - induced upregulation of TFF2 expression in gastric epithelial cells2004

    • Author(s)
      Shimada T. et al.
    • Journal Title

      FEBS 558

      Pages: 33-38

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Endoscopic Papillary Balloon Dilation for Treatment of Common Bile Duct Stones2004

    • Author(s)
      Watanabe H., Hiroshi H.et al.
    • Journal Title

      Hepatogastroenterology 51

      Pages: 652-657

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical evalution of granulocyte/monocyte apheresis therapy for active ulcerative colitis2004

    • Author(s)
      Kanke K., Hiroshi H.et al.
    • Journal Title

      Dig Liver Dis 36(12)

      Pages: 811-817

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese2004

    • Author(s)
      Kato A., Terano A.et al.
    • Journal Title

      Hepatol Res 30(2)

      Pages: 71-78

    • NAID

      10018025285

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transforming growth factor-β-induced stimulation of formation of collagen fiber network and anti-fibrotic effect of taurine in an in vitro model of hepatic fibrosis2004

    • Author(s)
      Kato J., Terano A.et al.
    • Journal Title

      Hepatol Res 30(1)

      Pages: 34-41

    • NAID

      10018025147

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification and characterization of taxilin isoforms2004

    • Author(s)
      Nogami S., Terano A.et al.
    • Journal Title

      Biochem Biophys Res Commun 319(3)

      Pages: 936-943

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intraportal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors2004

    • Author(s)
      Hashimoto T., Yoneda M.et al.
    • Journal Title

      Toxicol Apple Pharmacol 196(1)

      Pages: 1-10

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vitamin E Therapy in Patients With NASH2004

    • Author(s)
      Yoneda M. et al.
    • Journal Title

      Hepatology 39(2)

      Pages: 568-568

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 胃潰瘍診療ガイドラインにおけるGERDの考え方2004

    • Author(s)
      白川勝朗 他
    • Journal Title

      日本臨床 62

      Pages: 1559-1564

    • Related Report
      2004 Annual Research Report
  • [Publications] Fujii S, Terano A et al.: "Efficacy of surveillance and molecular markers for detection of ulcerative colitis-associated colorectal neoplasia."J Gastrenterol. 38(12). 1117-1125 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakai T, Terano A et al.: "Cyclooxygenase expression during Helicobacter pylori infection in Mongolian gerbils."Dig Dis Sci. 48(11). 2139-2146 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukui H, Terano A et al.: "Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in Mongolian gerbils"Lab Invest. 83(12). 1777-1786 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoneda M, Terano A et al.: "Thyrotropin-releasing hormone in the dorsal vagal complex stimulates hepatic blood flow in rats."Hepatology. 38(6). 1500-1507 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nogami S, Terano A et al.: "Interaction of taxilin with syntaxin which does not from the SNARE complex"Biochem Biophys Res Commun. 311(4). 797-802 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoneda M, Terano A et al.: "Involvement of calcitonin gene-related peptide and capsaicin-sensitive afferents in central thyrotropin-releasing hormone-induced hepatic cytoprotection."Eur J Pharmacol. 478(2-3). 173-177 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe H, Terano A et al.: "Pathophysiology of gastric acid secretion in patients with chronic renal failure : influence of Helicobacter pylori infection"J Intern Med. 254(5). 439-446 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada T, Terano A et al.: "Up-regulation of TFF expression by PPAR gamma ligands in gastric epithelial cells"Aliment Pharmacol Ther. suppl 1. 119-125 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawamata H, Terano A et al.: "Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.Tn-AT1, by cDNA microarray."Cancer Sci. 94(8). 699-706 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato Y, Terano A et al.: "Protective effect of central thyrotropin-releasing hormone on carbon tetrachloride-induced acute hepatocellular necrosis in rats."J Hepatol. 39(1). 47-54 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terano A: "The current status of GERD between the west and the east."J Gastroenterol. suppl 15:. 1-2 (2003)

    • Related Report
      2003 Annual Research Report

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

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