期刊
FASEB JOURNAL
卷 35, 期 7, 页码 -出版社
WILEY
DOI: 10.1096/fj.202002631RRR
关键词
apoptosis; cancer; carcinogenesis; D-dopachrome tautomerase; macrophage migration inhibitory factor; p53; skin; ultraviolet
资金
- Japan Society for the Promotion of Science [20K08686]
- Grants-in-Aid for Scientific Research [20K08686] Funding Source: KAKEN
The study showed that D-DT Tg mice developed tumors more rapidly than wild-type mice under chronic UVB exposure, with a higher incidence of tumors observed in D-DT Tg mice. The expression of p53, PUMA, and Bax in keratinocytes of D-DT Tg mice was lower compared to wild-type mice, indicating that D-DT overexpression may confer protection against UVB-induced apoptosis in keratinocytes. These findings suggest that D-DT plays a crucial role in photocarcinogenesis and could be a potential therapeutic target for preventing skin malignancies.
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. However, its role, unlike the role of MIF in photocarcinogenesis, is unknown. We therefore 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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