2020 Fiscal Year Final Research Report
Overexpression of D-dopachrome tautomerase increases ultraviolet B irradiation-induced skin tumorigenesis in mice
| Project/Area Number |
18K08293
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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 | University of Toyama |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
牧野 輝彦 富山大学, 学術研究部医学系, 准教授 (90359711)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | D-dopachrome tautomerase / MIF / ultraviolet / p53 / skin cancer / carcinogenesis / apoptosis |
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| Outline of Final Research Achievements |
Ultraviolet irradiation (UV) exposure is the leading factor underlying the development of skin malignancies. D-dopachrome tautomerase (D-DT), a functional homolog of macrophage migration inhibitory factor (MIF), has functional similarities to MIF. We explored the role of D-DT in photocarcinogenesis by developing D-DT transgenic (D-DT Tg) mice and provided a research model for future studies targeting D-DT. Chronic UVB exposure accelerated tumor development in D-DT Tg mice compared with wild-type (WT) mice, with a higher incidence of tumors observed in D-DT Tg mice than in WT mice. In D-DT Tg irradiated mouse keratinocytes, the p53, PUMA, and Bax expression was lower than that in WT mice. These results indicate that D-DT Tg overexpression confers prevention against UVB-induced apoptosis in keratinocytes. Taken together, these findings support D-DT as a functionally important cytokine in photocarcinogenesis and potential therapeutic target for the prevention of photocarcinogenesis.
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| Free Research Field |
皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
D-DTは光発癌における機能的に重要なサイトカインであり，光発癌予防のための治療標的になりうることが証明された．
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