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Relevance of genes involved in skin tissue formation to human diseases and its application for regenerative medicine.

Research Project

Project/Area Number 14370260
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionOkayama University

Principal Investigator

HUH Nam-ho  Okayama University, Graduate School of Medicine and Dentistory Department of Cell Biology, Professor, 大学院・医歯学総合研究科, 教授 (70173573)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Masahiro  Okayama University, Graduate School of Medicine and Dentistory Department of Cell Biology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (90116509)
TAKAISHI Mikiro  Okayama University, Graduate School of Medicine and Dentistory Department of Cell Biology, Research Associate, 大学院・医歯学総合研究科, 助手 (10303223)
KATAOKA Ken  Okayama University, Graduate School of Medicine and Dentistory Department of Cell Biology, Research Associate (2002-2003), 大学院・医歯学総合研究科, 助手 (10293317)
SAKAGUCHI Masakiyo  Okayama University, Graduate School of Medicine and Dentistory Department of Cell Biology, Research Associate (2004), 大学院・医歯学総合研究科, 助手 (70379840)
MOROHASHI Masaaki  Toyama Medical and Pharmaceutical University, Faculty of Medicine Department of Dermatology, Professor, 医学部, 教授 (50018719)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordsskin / growth regulation / differentiation / S100 / Ca / keratinization / Hornerin / stem cells / S100C / A11 / hornerin / profilaggrin / TGFβ / 増殖 / Profilaggrin / 骨髄 / calmin / 組織構築
Research Abstract

This research project is aiming to identify genes involved in the formation of skin and to develop therapeutic measures based on the molecular mechanisms of the gene products. Major results obtained are as follows.
1.Growth regulation of human keratinocytes : A novel pathway involving S100C/A11
We found that a Ca-binding protein S100C/A11 mediates the growth inhibitory signal of both high Ca and TGFβ which are representative growth suppressors for normal human keratinocytes. On exposure to high Ca or TGFβ, S100C/A11 was phosphorylated by PKCα and transferred to nuclei, where it induced p21/WAF1 through activation of Sp1. In addition to this common pathway, we showed that the well-known unique pathways, the NFAT1-mediated and Smad-mediated pathways for high Ca and TGFβ, respectively, were indispensable for the growth inhibition.
2.Keratinization of epidermal keratinocytes : Characterization of newly-isolated gene, hornerin
Hornerin is a newly isolated gene, which has common structural features with profilaggrin, a key protein for keratinization. In adult mouse, hornerin was expressed in stratified epithelial cells of the skin, tongue, esophagus, and forestomach. We also isolated and characterized the human ortholog. Unexpectedly, hornerin protein was not detected in normal adult trunk skin but induced in the regenerating epidermis and psoriatic epidermis.
3.Differentiation of adult bone marrow cells into skin cells
We established a skin reconstitution system by inoculating a suspension of mouse embryonic skin cells into a silicon chamber on the back of nude mice. We showed that adult mouse bone marrow cells were differentiated into skin cells including cells forming epidermis, hair follicles, and sebaceous glands when transplanted with the embryonic skin cells.
4.Isolation of stem cells from mouse embryonic skin
We isolated stem cells by inoculating mouse embryonic skin cells into a thermo-sensitive synthetic gel.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (32 results)

All 2005 2004 2003 Other

All Journal Article (17 results) Book (1 results) Publications (14 results)

  • [Journal Article] Identification of human hornerin and its expression in regenerating and psoriatic skin.2005

    • Author(s)
      Takaishi et al.
    • Journal Title

      Journal of Biological Chemistry 280(6)

      Pages: 1314-1318

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of human hornerin and its expression in regenerating and psoriatic skin.2005

    • Author(s)
      Takaishi M, Makino T, Morohashi M, Huh NH
    • Journal Title

      J Biol Chem. 280(6)

      Pages: 4696-4703

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of human homerin and its expression in regenerating and psoriatic skin.2005

    • Author(s)
      Takaishi et al.
    • Journal Title

      Journal of Biological Chemistry 280(6)

      Pages: 4696-4703

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PKCalpha mediates TGFbeta-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11.2004

    • Author(s)
      Sakaguchi et al.
    • Journal Title

      Journal of Cell Biology 164(7)

      Pages: 979-984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Introduction of an N-terminal peptide of S100C/A11 into human cells induces apoptotic cell death.2004

    • Author(s)
      Makino et al.
    • Journal Title

      Journal of Molecular Medicine 82(9)

      Pages: 612-620

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] PKCalpha mediates TGFbeta-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11.2004

    • Author(s)
      Sakaguchi M, Miyazaki M, Sonegawa H, Kashiwagi M, Ohba M, Kuroki T, Namba M, Huh NH
    • Journal Title

      J Cell Biol. 164(7)

      Pages: 979-984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Introduction of an N-terminal peptide of S100C/A11 into human cells induces apoptotic cell death.2004

    • Author(s)
      Makino E, Sakaguchi M, Iwatsuki K, Huh NH
    • Journal Title

      J Mol Med. 82(9)

      Pages: 612-620

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] PKCalpha mediates TGFbeta-induced growth inhibition of human keratinocytes via phosphorvlation of S100C/A11.2004

    • Author(s)
      Sakaguchi et al.
    • Journal Title

      Journal of Cell Biology 164(7)

      Pages: 979-984

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of interferon regulatory factor 1 and S100C/A11 in growth inhibition by transforming growth factor beta 1 in human hepatocellular carcinoma cells2004

    • Author(s)
      Miyazaki
    • Journal Title

      Cancer Research 64(12)

      Pages: 4155-4161

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Propagation of adult rat bone marrow-derived hepatocyte-like cells by serial passages in vitro.2004

    • Author(s)
      Miyazaki et al.
    • Journal Title

      Cell Transplantation 13(4)

      Pages: 385-391

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma2004

    • Author(s)
      Kurose et al.
    • Journal Title

      Journal of Urology 171(3)

      Pages: 1314-1318

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of hornerin in stratified squamous epithelium in the mouse. A comparative analysis with profilaggrin.2003

    • Author(s)
      Makino et al.
    • Journal Title

      Journal of Histochemistry and Cytochemistry 51(4)

      Pages: 485-492

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Participation of adult mouse bone marrow cells in reconstitution of skin.2003

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

      American Journal of Pathology 163

      Pages: 1227-1231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] S100C/A11 Is a Key Mediator of Ca^<++>-induced Growth Inhibition of Human Epidermal Keratinocytes.2003

    • Author(s)
      Sakaguchi et al.
    • Journal Title

      Journal of Cell Biology 163(4)

      Pages: 825-835

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of hornerin in stratified squamous epithelium in the mouse : a comparative analysis with profilaggrin.2003

    • Author(s)
      Makino T, Takaishi M, Toyoda M, Morohashi M, Huh NH
    • Journal Title

      J Histochem Cytochem. 51(4)

      Pages: 485-492

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Participation of adult mouse bone marrow cells in reconstitution of skin.2003

    • Author(s)
      Kataoka K, Medina RJ, Kageyama T, Miyazaki M, Yoshino T, Makino T, Huh NH
    • Journal Title

      Am J Pathol. 163(4)

      Pages: 1227-1231

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes.2003

    • Author(s)
      Sakaguchi M, Miyazaki M, Takaishi M, Sakaguchi Y, Makino E, Kataoka N, Yamada H, Namba M, Huh NH
    • Journal Title

      J Cell Biol. 163(4)

      Pages: 825-835

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 細胞培養なるほどQ&A2004

    • Author(s)
      許 南浩・編
    • Total Pages
      221
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Publications] Sakaguchi M, Miyazaki M, Sonegawa H, Kashiwagi M, Namba M, Huh N et al.: "PKCα mediates TGFβ-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11"Journal of Cell Biology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyazaki M, Masaka T, Akiyama I, Nakashima E, Sakaguchi M, Huh N: "Propagation of adult rat bone marrow-derived hepatocyte-like cells by serial passages in vitro"Cell Transplantation. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakaguchi M, Miyazaki M, Takaishi M, Namba M, Huh N et al.: "S100C/A11 Is a key mediator of Ca^<++>-induced growth inhibition of human epidermal keratinocytes"Journal of Cell Biology. 163. 825-835 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakajima A, Kataoka K, Hong M, Sakaguchi M, Huh N: "BRPK, a novel protein kinase showing increased expression in mouse cancer cell lines with higher metastatic notential"Cancer Letters. 201. 195-201 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kataoka K, Medina RJ, Kageyama T, Makino T, Huh N et al.: "Participation of Adult Mouse Bone Marrow Cells in Reconstitution of Skin"American Journal of Pathology. 163. 1227-1231 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibakura M, Niiya K, Kiguchi T, Kitajima I, Niiya M, Asami N, Huh N et al.: "Induction of interleukin-8 and monocyte chemoattractant protein-1 by doxorubicin in human small-cell lung carcinoma cells"Int ernational Journal of Cancer. 103. 380-386 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyazaki M, Kataoka K, Medina RJ, Kageyama T, Huh N: "Differentiation of bone marrow cells in culture and in vivo. International Congress Serics 1718"Elsevier Sciences B.V.. 4 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kataoka K, Huh N: "A novel β1,3-N-acetylglucosaminyltransferase involved in invasion of cancer cells as assayed in vitro"Bichem Biophys Res Commun. 294(4). 843-848 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogawa H, Gomi T, Takusagawa F, Masuda T, Goto T, Kan T, Huh NH: "Evidence for a dimeric structure of rat liver serine dehydratese"Int. J Biochem Cell Biol. 34(5). 533-543 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazaki M, Akiyama I, Sakaguchi M, Nakashima E., Okada, M. et al.: "Improved conditions to induce hepatocytes from rat bone marrow cells in culture"Bichem Biophys Res Commun. 298(1). 24-30 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takaishi M, Ishisaki Z, Yoshida T, Takata Y, Huh N: "Expression of calmin, a novel developmentally regulated brain protein with calponin-homology domains"Brain Res Mol Brain Res.. 112(1-2). 146-152 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Makino T, Takaishi M, Toyoda M, Morohashi M, Huh N: "Expression of hornerin in stratified squamous epithelium in the mouse. A comparative analysis with profilaggrin"J Histochem Cytochem. 51(4). 485-492 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toyoda M.Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M: "Nerve growth factor and substance P are useful plasma markers of disease activity of atopic dermatitis"Br J Dermatol. 147(1). 71-79 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 許 南浩: "バイオ人工皮膚.現代化学増刊「再生医学・再生医療」、室田誠逸編"東京化学同人. 211-213 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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