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A STUDY ON REGULATORY MECHANISM OF GROWTH AND DIFFERENTIATION IN HUMAN KERATINOCYTES BY GROWTH FACTORS.

Research Project

Project/Area Number 06670863
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionEHIME UNIVERSITY SCHOOL OF MEDICINE (1995)
Osaka University (1994)

Principal Investigator

HASHIMOTO Koji  EHIME UNIVERSITY SCHOOL OF MEDICINE,DERMATOLOGY,PROFESSOR, 医学部, 教授 (00110784)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsGROWTH FACTORS / EGF / HB-EGF / EPIDERMIS / PSORIASIS / TGF-BETA / KERATINOCYTE / HB-EGF、 / TGH-alpha、 / 細胞成長因子、 / EGFファミリー細胞成長因子、 / TGF-beta、 / ルシフェラーゼ、 / 分化誘導、
Research Abstract

(1) EGF family growth factors
We investigated a role of HB-EGF,a new member of EGF family growth factor, in the regulatory mechanism of human keratinocyte growth. HB-EGF stimulated keratinocyte growth and keratinocytes produced HB-EGF.This showed that HB-EGF is an autocrine growth factor for human keratinocytes like TGF-alpha and amphiregulin. Furthermore, addition of HB-EGF induced production of TGF-alpha and addition of TGF-alpha increased production of HB-EGF.Taken together, auto-and cross-induction mechanism of EGF family growth factor such as HB-EGF,TGF-alpha and amphiregulin works in human keratinocytes. Localization of HB-EGF in normal and psoriatic epidermis was studied immunohistochemically. HB-EGF was present through whole epidermis including basal cells in normal skin. In psoriatic epidermis, the staining intensity of HB-EGF was markedly increased compared to normal epidermis although the localization was similar in both epidermis.
(2) TGF-beta family growth factors
We investigated the localization of TGF-beta isoforms (1,2 and 3) immunohistochemically, using antibodies specific to the precursor forms of each isoform. TGF-beta 2 was present mainly in the intercellular space of whole epidermis in normal skin. In contrast, the staining intensity of TGF-beta 2 was absent or decreased markedly in psoriatic epidermis.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Hashimoto K et al.: "Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes." J Biological Chemistry. 269. 20060-20066 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 橋本公二: "細胞成長因子による表皮増殖の制御-その二面性について-" 日本皮膚科学会雑誌. 104. 1632-1634 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Wataya-Kaneda M et al.: "Differential localization of TGF-beta-precursor isotypes in normal human skin" Journal of Dermatological Science. 8. 38-44 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi T et al.: "Dephosphorylation of the retinoblastoma gene product induced by differentiation and its relevancy to growth inhibition in normal human keratinocytes." Journal of Dermatological Science. 8. 171-177 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mizutani H.et al.: "Functional and immunoreactive thrombomodulin expressed by keratinocytes." Journal of Investigative Dermatology. 103. 825-828 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi T et al.: "Effect of donor age on the phosphorylation of the retinoblastoma gene product in cultured human keratinocytes." Journal of Dermatological Science. 9. 59-63 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] HASHIMOTO K,HIGASHIYAMA S,ASADA H,HASHIMURA,E.KOBAYASHI,T.ETAL: "HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH FACTOR IS AN AUTOCRINE GROWTH FACTOR FOR HUMAN KERATIOCYTES" J BIOL CHEM. 269. 20060-20066 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] TAKADA A,HASHIMOTO K,YOSHIKAWA K.: "GROWTH-PROMOTING EFFECT OF BACTERIAL PRODUCTS FROM CLOSTRIDIUM PERFRINGENS ON HUMAN KERATINOCYTES" J DERMATOL. 21. 539-545 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] HASHIMOTO K.: "GROWTH REGULATION OF EPIDERMIS BY GROWTH FACTORS-TWO ASPECTS OF THEIR FUNCTION" J JAP DERMATOL ASSO. 104. 1632-1634 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] WATAYA-KANEDA M,HASHIMOTO K,KATO M,MIYAZONO K,YOSHIKAWA K.: "DIFFERENTIAL LOCALIZATION OF TGF-BETA-PRECURSOR ISOTYPES IN NORMAL HUMAN SKIN" J DERMATOL SCI. 8. 38-44 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] KOBAYASHI T,HASHIMOTO K,YOSHIKAWA K.: "DEPHOSPHORYLATION OF THE RETINOBLASTOMA GENE PRODUCT INDUCED BY DIFFERENTIATION AND ITS RELEVANCY TO GROWTH INHIBITION IN NORMAL HUMAN KERATINOCYTES" J DERMATOL SCI. 8. 171-177 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] MIZUTANI H.HAYASHI T,NOGUCHI N,OHYANAGI S,HASHIMOTO K,ET AL.: "FUNCTIONAL AND IMMUNOREACTIVE THROMBOMODULIN EXPRESSED BY KERATINOCUTES" J INVEST DERMATOL. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] HASHIMOTO K.: "DISCOVERY OF NEW FUNCTIONS OF VITAMIN AND BIOFACTOR (10) PSORIASIS AND VITAMIN D" VITAMIN. 69. 33-38 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] HASHIMOTO K.: "CULTURED EPIDERMAL SHEET GRAFT-DREAM OF CELL BANK SYSTEM- HIFUBYOH-SHINRYYOH" 17. 432-436 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] KOBAYASHI T,HASHIMOTO K,SUDO K,NISHIOTO S, YOSHIKAWA K.: "EFFECT OF DONOR AGE ON THE PHOSPHORYLATION OF THE RETINOBLASTOMA GENE PRODUCTIN CULTURED HUMAN KERATINOCYTES" J DERMATOL SCI. 9. 59-63 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] KOBAYASHI T,HASHIMOTO K,YOSHIKAWA K.: "GROWTH INHIBITION OF HUMAN KERATINOCYTES BY MC903 (CALCIPOTRIOAL) IS LINKED TO DEPHOSPHORYLATION OF RETINOBLASTOMA GENE PRODUCT" J EUR ACADERMATOL VENEROL. 5. 132-138 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hashimoto K et al.: "Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes." J Biological Chemistry. 269. 20060-20066 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 橋本公二: "細胞成長因子による表皮増殖の制御-その二面性について-" 日本皮膚科学会雑誌. 104. 1632-1634 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Wataya-Kaneda M et al.: "Differential localization of TGF-beta-precursor isotypes in normal human skin" Journal of Dermatological Science. 8. 38-44 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kobayashi T et al.: "Dephosphorylation of the retinoblastoma gene product induced by differentiation and its relevancy to growth inhibition in normal human keratinocytes." Journal of Dermatological Science. 8. 171-177 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mizutani H.et al.: "Functional and immunoreactive thrombomodulin expressed by keratinocytes." Journal of Investigative Dermatology. 103. 825-828 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kobayashi T et al.: "Effect of donor age on the phosphorylation of the retinoblastoma gene product in cultured human keratinocytes." Journal of Dermatological Science. 9. 59-63 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Koji Hashimoto et al.: "Heparin-binding epidrmal growth factor-like growth factor is an autocrine growth factor for human keratinocytes." Jouranl of Biological Chemistry. 269. 20060-20066 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 橋本公二: "細胞成長因子による表皮増殖の制御" 日本皮膚科学会雑誌. 104. 1632-1634 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mari Higashiyama,Koji Hashimoto et al.: "Differential expression of transforming growth factor-a(TGF-a)and EGF receptor in transitional area of psoriatic epidermis." Journal of Dermatological Science. 7. 45-53 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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