| Project/Area Number |
03454273
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Osasa University |
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Principal Investigator |
YOSHIKAWA Kunihiko Osaka Univ., Dept.of Professor, 医学部, 教授 (20110851)
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| 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)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| 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)
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| Keywords | Keratinocytes / 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 |
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| 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.
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