| Project/Area Number |
18K08267
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Osaka City University |
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Principal Investigator |
KATAYAMA ICHIRO 大阪市立大学, 大学院医学研究科, 特任教授 (80191980)
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| Co-Investigator(Kenkyū-buntansha) |
楊 伶俐 大阪市立大学, 大学院医学研究科, 特任講師 (40711784)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 酸化ストレス / メラノサイトニッチ / 細胞接着 / 肥満細胞 / GPNMB / SCF / TNFα / TGFβ / 白斑 / 表皮メラノサイト / ニッチ |
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| Outline of Final Research Achievements |
We screened the expression of cell adhesion related -proteins in the lesional skin of vitiligo and found that melanocyte marker protein, GPNMB is expressed in basal keratinocytes of the normal skin and disappeared in the vitiligo skin under possible regulation by IFNγ induced -JAK2 confirmed by in vitro study （Sci Rep. 2020 Mar 18;10(1):4930）. UV irradiation significantly downregulated GPNMB expression in a dose dependent fashion with upregulated expression of SCF and TNFα. In addition to UV stress, knockdown of GPNMB in keratinocyte by siRNA significantly upregulated SCF production which is confirmed by RT-PCR and WB analysis. These results suggest that induction of vitiligo through stress and/or autoimmune mediated melanocyte loss in the vitiligo is correlated with increased inflammatory cytokine production possibly related to decreased expression of GPNMB by keratinocytes and provide new therapeutic strategies for the refractory vitiligo.
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| Academic Significance and Societal Importance of the Research Achievements |
白斑病変部ケラチノサイトでGPNMBの発現が低下しており、in vitroの解析でIFNγがJAK2
依存性にGPNMBの発現を制御していること、さらにGPNMBが細胞成長因子や炎症性サイトカインの発現制御御をしている事を見いだし、現在開発が進められているJAK阻害薬の標的の一つとなる可能性を考えており、今後の白斑治療薬開発に貢献しうる成果と考える。
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