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Analysis of regulatory mechanism of various growth factors in the growth and differentiation of human keratinocytes and fibroblasts

Research Project

Project/Area Number 03454273
Research Category

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

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionOsasa University

Principal Investigator

YOSHIKAWA Kunihiko  Osaka Univ., Dept.of Professor, 医学部, 教授 (20110851)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Toshikazu  Osaka Univ., Dept.of Tumor Biochem, Professor, 医学部, 教授 (00049397)
HIGASHIYAMA Mari  Osaka Univ., Dept.of Dermatology Associate Professor, 医学部, 助手 (40228713)
HASHIMOTO Koji  Osaka Univ., Dept.of Dermatology Associate Professor, 医学部, 助教授 (00110784)
藤川 昌和  大阪大学, 医学部, 助手 (80228973)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsKeratinocytes / EGF family growth factors / TGF-alpha / amphiregulin / HB-EGF / TGF-beta / EDIN / Psoriasis / アンフィレグリン / プロテイン・キナーゼC / TGF-βレセプター / TGFーα / TGFーβ / TNF / HGF5,表皮ケラチノサイト / 創傷モデル / in situ hybridization / 免疫組織化学 / Down Regulation
Research Abstract

The summary of our research results was classified into three groups : 1) EGF family growth factors, 2) TGF-beta, 3) Epidermal cell diferrentiation inhibitor(EDIN). Concerning to EGF family growth factors, it was known that TGF-alpha and amphiregulin were autocrine growth factors for human keratinocytes. They stimulate the growth of human ketatinocytes and produced by human keratinocytes. In this study, we showed that heparin-binding EGF-like growth factor(HB-EGF), a new member of EGF family growth factor, is also an autocrine growth factor for human keratinocytes. The localization of HB-EGF in normal and psoriatic epidermis was also shown by immunohistochemical methods. Interestingly, an mutual stimulatory mechanism of these EGF family growth factors was revealed : the addtion of HB-EGF or TGF-alpha increased all of HB-EGF mRNA, TGF-alpha mRNA and amphiregulin mRNA.So, this is a very effecttive mechanism for induction of autocrine EGF family growth factors. It will be one of the main aims in the future study on growth regulation of human keratinocytes. Concerning to TGF-beta, we identified the localization of TGF-beta isoforms in the human skin. In the normal human skin, TGF-beta2 is localized in the epidermis and TGF-beta3 is localized mainly in the upper dermis. Interestingly, the staining intensity of TGF-beta2 was decreased in the epidermis of psoriatic lesions. This may be correlated with the epidermal hyperplasia in psorisis. Concerning to EDIN, it was purified from the supernatant of Staphylococcus aureus. It inhibits the differentiation of human ketatinocytes. We demonstrated that EDIN ADP-ribosylates rho protein, one of small G proteins and inserts its effect.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Teruaki Kobayashi,Koji Hashimoto,Kunihiko Yoshikawa,et al.: "Analysis of Interleukin 6 Receptor on Normal Human Keratinocytes by Digital Imaging Fluorescence Microscopy" The Journal of Dermatology. 20. 585-587 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Teruaki Kobayashi Koji Hashimoto Kunihiko Yoshikawa: "Growth Inhibition of Human Keratinocytes by 1,25-Dihydroxyvitamin D_3 is Linked to Dephosphorylation of Retinoblastoma Gene Product." Biochemical and Biophysical Research Communications. 196. 487-493 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 橋本公二,東山真里,金田真理,吉川邦彦: "表皮細胞に関する細胞成長因子と受容体" 皮膚科の臨床. 35. 1363-1369 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 橋本公二,東山真里,坂井靖夫,吉川邦彦: "培養表皮細胞移植" 皮膚科の臨床. 34. 913-917 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Koji Hashimoto Kunihiko Yoshikawa: "The Growth Regulation of Keratinocytes" The Journal of Dermatology. 19. 648-651 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Motoyuki Sugai Koji Hashimoto Kunihiko Yoshikawa et al.: "Epidermal Cell Differentiation Inhibitor ADP-ribosylates Small GTP-binding Proteins and Induces Hyperplasia of Epidermis" The Journal of Biological Chemistry. 267. 2600-2604 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Koji Hashimoto,Kunio Matsumoto,Kunihiko Yoshikawa: "The Biology of the Epidermis" Elsevier Science Publishers B.V., (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] KOBAYASHI,T., HASHIMOTO,K., YOSHIKAWA,K.: "GROWTH INHIBITON OF HUMAN KERATINOCYTES BY 1,25-DIHYDROXYVITAMIN D_3 IS LINKED TO DEPHOSPHORYLATION OF RETINOBLASTOMA GENE PRODUCT" BIOCHEM BIOPHYS RES COMM. 196. 487-493 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] KOBAYASHI,T., HASHIRO,M., HASHIMOTO,K., YOSHIKAWA,K.: "ONCOGENE,SUPPRESSOR ONCOGENE AND THEIR PROTEIN PRODUCTS (JAPANESE)" NIPPIKAISHI. 103. 1610-1613 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HASHIMOTO,K., HIGASHIYAMA,M., KANEDA,M., YOSHIKAWA,K.: "GROWTH FACOTRS AND THEIR RECEPTORS IN EPIDERMAL CELLS(JAPANESE)" HIFUKANORINNSHO. 35. 1363-1369 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] KOBAYASHI,T., HASHIMOTO,K., MATSUMOTO,K., YOSHIZAKI,K., YOSHIKAWA,K.: "ANALYSISI OF THE INTERLEUKIN 6 RECEPTOR OF NORMAL HUMAN KERATINOCYTES BY DIGITAL IMAGING FLUORESCENCEMICROSCOPY" JOURNAL OF DERMATOLOGY. 20. 585-587 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] SUGAI,M., HASHIMOTO,K., KIKUCHI,A., INOUE,S., OKUMURA,H., MATSUMOTO,K., GOTO,Y., OHGAI,H., MORIISHI,K., SHUTO,B., YOSHIKAWA,K., SUGINAKA,H., TAKAI,H.: "EPIDERMAL CELL DIFFERENTIATION INHIBITOR ADP-RIBOSYLATES SMALL GTP-BINDING PROTEINS AND INDUCES HYPERPLASIA OF EPIDERMIS" JOURNAL OF BIOLOBICAL CHEMISTRY. 267. 2600-2604 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HIGASHIYAMA,M., HASHIMOTO,K., TAKADA,A., FUJITA,K., KIDO,K.YOSHIKAWA,K.: "THE ROLE OF GROWTH FACTOR IN WOUND HEALING" JOURNAL OF DERMATOLOGY. 19. 676-679 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HASHIMOTO,K., YOSHIKAWA,K.: "THE GROWTH REGULATION OF KERATINOCYTES" JOURNAL OF DERMATOLOGY. 19. 648-651 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HASHIMOTO,K., HIGASHIYAMA,M.SAKAI,Y., YOSHIKAWA,K.: "TRANSPLANTATION OF CULTURED EPIDERMAL SHEETS(JAPANESE)" HIFUKANORINNSHO. 34. 913-917 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HASHIMOTO,K., MATSUMOTO,K., YOSHIKAWA,K.: "THE EFFECT OF VITAMIN D_3 ON HUMAN KERATINOCYTES" IN THE BIOLOGY OF THE EPIDERMIS (EDS., OHKAWARA,A., MCGUIRE J). 123-131 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 小林照明、羽白誠、橋本公二、吉川邦彦: "ケラチノサイトの増殖調節 増殖関連蛋白-癌遺伝子,癌抑制遺伝子とその遺伝子産物について-" 日本皮膚科学会雑誌. 103. 1610-1613 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 橋本公二、東山真里、金田真理、吉川邦彦: "表皮細胞に関する細胞成長因子と受容体" 皮膚科の臨床. 35. 1363-1369 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Teruaki Kobayashi,Koji Hashimoto,Kunihiko Yoshikawa: "Growth Inhibition of Human Keratinocytes by 1,25-Dihyroxyvitamin D_3 is Linked to Dephosphorylation of Retinoblastoma Gene Product" Biochemical and Biophysical Research Communications. 196. 487-493 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Teruaki Kobayashi,Kunihiko Yoshikawa,et.al.: "Analysis of Interleukin 6 Receptor Normal Human Keratinocytes by Digital Imaging Fluorescence Microscopy" The Journal of Dermatology. 20. 585-587 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 東山 真里,橋本 公二 吉川 邦彦,松本 邦夫: "皮膚科領域とビタミンD" CLINICAL CALCIUM. 2. 100-106 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Sugai K.Hashimoto K.Yoshikawa,et al.: "Epidermal Cell Differentiation Inhibitor ADP-ribosylates Small GTP-binding Proteins and Induces Hyperplasia of Epidermis" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 267. 2600-2604 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 橋本 公二,東山 真里 坂井 靖夫,吉川 邦彦: "培養表皮細胞移植 ー現状と未来ー" 皮膚科の臨床. 34. 913-917 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 橋本 公二,東山 真里 坂井 靖夫,吉田 邦彦: "培養表皮細胞の治療への応用" 臨床皮膚科. 46. 123-127 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 橋本 公二,菅井 基行 吉川 邦彦: "黄色ブドウ球菌の産生する表皮細胞分化抑制因子 ーepidermal cell differentiation inhibitor(EDIN)について" 皮膚病診療. 14. 954-958 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Higashiyama;K.Matsumoto;K.Hashimoto;K.Yoshikawa: "Increased production of transforming growth factorーα in psoriatiac epidermis" J.Dermatol.18. 117-119 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hashiro;K.Matsumoto;K.Hashimoto;K.Yoshikawa: "Stimulation of fibronectin secretion in cultured human keratinocytes by transforming growth factorーβ not by other growth inhibitory substances" J.Dermatol.18. 252-257 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Matsumoto;Y.Azuma,et al.: "Involvement of endogenously produced 1,25ーhydroxyvitamin Dー3 in the growth and differentiation of human keratinocytes" Biochem.Biopys.Acta. 1092. 311-318 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Matsumoto;K.Hashimoto;K.Yoshikawa;T.Nakamura: "Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor" Exp.Cell Res.196. 114-120 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 橋本 公二,東山 真里,吉川 邦彦: "ビタミンD_3による乾癬の治療" 皮膚科の臨床. 33. 1031-1035 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 東山 真里,橋本 公二,吉川 邦彦,橋本 邦夫: "皮膚科領域とビタミンD" Clinical Calcium. 2. 100-106 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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