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2004 Fiscal Year Final Research Report Summary

Study for the molecular mechanisms involved in regeneration and repair of injured gastrointestinal mucosa

Research Project

Project/Area Number 14370079
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionUniversity of Miyazaki (2004)
宮崎医科大学 (2002-2003)

Principal Investigator

KATAOKA Hiroaki  University of Miyazaki, Department of Pathology, Professor, 医学部, 教授 (10214321)

Co-Investigator(Kenkyū-buntansha) ITOH Hiroshi  University of Miyazaki, Department of Pathology, Associate Professor, 医学部, 助教授 (80253847)
Project Period (FY) 2002 – 2004
Keywordshepatocyte growth factor(HGF) / HGF activator / HAI-1 / HAI-2 / H2RSP / gastrointestinal mucosal regeneration / differentiation / knockout mouse
Research Abstract

Cell surface proteolysis is an important mechanism for the generation of biologically active proteins that mediate a diverse range of cellular functions. We have studied the roles of proteinases and integral-membrane proteinase inhibitors in this process for many years.
In this project, we studied possible roles of cellular surface interactions of proteinases and integral-membrane proteinase inhibitors in regeneration of injured gastrointestinal mucosae, focusing on the activation mechanism of hepatocyte growth factor(HGF), a multifunctional growth factor having important roles in the regeneration of gastrointestinal tracts. For this purpose, we have generated knockout mice of HGF activator (a proteinase that is responsible for the activation of HGF in injured tissue) and its cognate integral-membrane inhibitor, HAI-1(HGF activator inhibitor type 1). The overall results indicated that HGF activator has important role in early regeneration phase of intestinal mucosa, called restitution. … More Indeed, initial regeneration of injured intestinal mucosa was significantly impaired in HGF activator-deficient mice. On the other hand, HAI-1 knockout mice died in early embryonic stage (around E10.5). This lethal point was obviously earlier than that of HGF-deficient mice. Detailed histological analyses indicated that HAI-1 knockout mice show severely impaired formation of the labyrinth layer. Therefore, HAI-1 might have yet undefined, but very important biological roles in vivo.
In this project, we also have identified a novel small peptide, namely H2RSP. H2RSP is expressed in the gastrointestinal epithelial cells. This molecule contains nuclear translocation signal domain. The localization of H2RSP was intracytoplasmic in proliferating epithelial cells. However, it was translocated into the nuclei in differentiated epithelial cells. Thus, it was assumed that the translocation of H2RSP into the nuclei might be involved in a signal for the transition from cellular proliferation to terminal differentiation of the epithelium. Less

  • Research Products

    (37 results)

All 2005 2004 2003 2002 Other

All Journal Article (37 results)

  • [Journal Article] Diverse roles of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in the growth of glioblastoma cells in vivo.2005

    • Author(s)
      Miyata S, Kataoka H, et al.
    • Journal Title

      Cancer Letters (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is required for branching morphogenesis in the chorioallantoic placenta.2005

    • Author(s)
      Tanaka H, Kataoka H, et al.
    • Journal Title

      Mol.Cell.Biol. 25(in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are expressed by tubular epithelium in kidney and downregulated in renal cell carcinoma.2004

    • Author(s)
      Yamauchi M, Kataoka H, et al.
    • Journal Title

      J.Urology 171

      Pages: 890-896

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator.2004

    • Author(s)
      Tjin EPM, Kataoka H, et al.
    • Journal Title

      Blood 104

      Pages: 2172-2175

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Paradoxically enhanced immunoreactivity of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in cancer cells at the invasion front.2004

    • Author(s)
      Nagaike K, Kataoka H, et al.
    • Journal Title

      Cancer Science 95

      Pages: 728-735

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regeneration of injured intestinal mucosa is impaired in hepatocyte growth factor activator-deficient mice.2004

    • Author(s)
      Itoh H, Kataoka H, et al.
    • Journal Title

      Gastroenterology 127

      Pages: 1423-1435

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue.2004

    • Author(s)
      Inoue T, Kataoka H, et al.
    • Journal Title

      Cancer Science 95

      Pages: 803-808

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Establishment and characterization of a new human glioblastoma cell line, NYGM.2004

    • Author(s)
      Nuki Y, Kataoka H, et al.
    • Journal Title

      Human Cell 17

      Pages: 145-150

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of heptocyte growth factor/scatter factor is required in colorectal carcinoma and injured intestinal mucosa.2004

    • Author(s)
      Itoh H, Kataoka H, et al.
    • Journal Title

      Recent Res.Devel.Histopathol. 4

      Pages: 1-16

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 消化管粘膜上皮再生における肝細胞増殖因子活性化因子(HGFA)の役割(ノックアウトマウスを用いた解析)2004

    • Author(s)
      伊藤浩史, 片岡寛章, 他
    • Journal Title

      消化器と免疫 40

      Pages: 12-21

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hepatocyte growth factor activator inhibitor type 1(HAI-1) and type 2(HAI-2) are expressed by tubular epithelium in kidney and downregulated in renal cell carcinoma.2004

    • Author(s)
      Yamauchi M, et al.
    • Journal Title

      J.Urol. 171

      Pages: 890-896

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Multiple myeloma cells catalyze hepatocyte growth factor(HGF) activation by secreting the serine protease HGF-activator.2004

    • Author(s)
      Tjin EPM, et al.
    • Journal Title

      Blood 104

      Pages: 2172-2175

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Paradoxically enhanced immunoreactivity of hepatocyte growth factor activator inhibitor type 1(HAI-1) in cancer cells at the invasion front.2004

    • Author(s)
      Nagaike K, et al.
    • Journal Title

      Cancer Sci. 95

      Pages: 728-735

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regeneration of injured intestinal mucosa is impaired in hepatocyte growth factor activator-deficient mice.2004

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

      Gastroenterology 127

      Pages: 1423-1435

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue.2004

    • Author(s)
      Inoue T, et al.
    • Journal Title

      Cancer Sci. 95

      Pages: 803-808

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment and characterization of a new human glioblastoma cell line, NYGM.2004

    • Author(s)
      Nuki Y, et al.
    • Journal Title

      Human Cell 17

      Pages: 145-150

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activation of heptocyte growth factor/scatter factor is required hi colorectal carcinoma and injured intestinal mucosa.2004

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

      Recent Res.Devel.Histopathol. 4

      Pages: 1-16

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of transcripts generated from mouse hepatocyte growth factor activator inhibitor type 2 (HAI-2) and HAI-2-related small peptide (H2RSP) genes : chimeric mRNA transcribed from both HAI-2 and H2RSP genes is detected in human but not in mouse.2003

    • Author(s)
      Naganuma S, Kataoka H, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 302

      Pages: 345-353

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A positive immunoselection method to isolate villous cytotrophblast cells from first trimester and term placenta to high purity.2003

    • Author(s)
      Potogens AJG, Kataoka H, et al.
    • Journal Title

      Placenta 24

      Pages: 412-423

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma.2003

    • Author(s)
      Fukai K, Kataoka H, et al.
    • Journal Title

      Cancer Research 63

      Pages: 8674-8679

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor2003

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

      Cancer Metast.Rev. 22

      Pages: 223-236

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of cancer cell-stroma interaction in invasive growth of cancer cells.2003

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

      Human Cell 16

      Pages: 1-14

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A positive immunoselection method to isolate villous cytotrophblast cells from first trimester and term placenta to high purity.2003

    • Author(s)
      Potogens AJG, et al.
    • Journal Title

      Placenta 24

      Pages: 412-423

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hepatocyte growth factor activator inhibitor 2/placental bikunin(HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma2003

    • Author(s)
      Fukai K, et al.
    • Journal Title

      Cancer Res. 63

      Pages: 8674-8679

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Roles of hepatocyte growth factor(HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor.2003

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

      Cancer Metast.Rev. 22

      Pages: 223-236

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mouse hepatocyte growth factor (HGF) activator inhibitor type 2 lacking the first Kunitz domain potently inhibits the HGF activator.2002

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

      Biochem.Biophys.Res.Commun. 290

      Pages: 1096-1100

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in human testis : Identification of a distinct transcription start site for the HAI-2 gene in testis.2002

    • Author(s)
      Yamauchi M, Kataoka H, et al.
    • Journal Title

      Biol.Chem. 383

      Pages: 1953-1957

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration.2002

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

      Pathology Int. 52

      Pages: 89-102

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Roles of hepatocyte growth factor activator (HGFA) and its inhibitor HAI-1 in the regeneration of injured gastrointestinal mucosa.2002

    • Author(s)
      Itoh H, Kataoka H, et al.
    • Journal Title

      J.Gastroenterolo. 37

      Pages: 15-21

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immunohistochemical analysis of hepatocyte growth factor activator and its inhibitor HAI-1 : Implication for regeneration of injured tissue and tumor progression.2002

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

      Recent Res.Devel.Histopathol. 1

      Pages: 67-76

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mouse hepatocyte growth factor(HGF) activator inhibitor type 2 lacking the first Kunitz domain potently inhibits the HGF activator.2002

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

      Biochem.Biophys.Res.Commun. 290

      Pages: 1096-1100

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of hepatocyte growth factor activator inhibitor type 2(HAI-2) in human testis : Identification of a distinct transcription start site for the HAI-2 gene in testis.2002

    • Author(s)
      Yamauchi M, et al.
    • Journal Title

      Biol.Chem. 383

      Pages: 1953-1957

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration.2002

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

      Pathol.Int. 52

      Pages: 89-102

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Roles of hepatocyte growth factor activator(HGFA) and its inhibitor HAI-1 in the regeneration of injured gastrointestinal mucosa.2002

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

      J.Gastroenterol. 37

      Pages: 15-21

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of transcripts generated from mouse hepatocyte growth factor activator inhibitor type 2(HAI-2) and HAI-2-related small peptide(H2RSP) genes : chimeric mRNA transcribed from both HAI-2 and H2RSP genes is detected in human but not in mouse.2002

    • Author(s)
      Naganuma S, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 302

      Pages: 67-76

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Diverse roles of hepatocyte growth factor activator inhibitor type 1(HAI-1) in the growth ofglioblastoma cells in vivo.

    • Author(s)
      Miyata S, et al.
    • Journal Title

      Cancer Lett. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hepatocyte growth factor activator inhibitor type 1(HAI-1) is required for branching morphogenesis in the chorioallantoic placenta.

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

      Mol.Cell.Biol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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