Overexpression of D-dopachrome tautomerase increases ultraviolet B irradiation-induced skin tumorigenesis in mice
Overexpression of D-dopachrome tautomerase increases ultraviolet B irradiation-induced skin tumorigenesis in mice
复制标题
D-多巴色素互变异构酶的过度表达增加了紫外线 B 照射诱导的小鼠皮肤肿瘤发生
DOI：
10.1096/fj.202002631rrr
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发表时间：
2021
期刊：
影响因子：
4.8
通讯作者：
Shimizu T
中科院分区：
文献类型：
--
作者：
Yoshihisa Y;Rehman MU;Andoh T;Tabuchi Y;Makino T;Shimizu T
紫外线照射（UV）暴露是皮肤恶性肿瘤发生的主要因素。 D-多巴色素互变异构酶（D-DT）是巨噬细胞迁移抑制因子（MIF）的功能同源物，与 MIF 具有功能相似性。然而，与 MIF 在光致癌作用中的作用不同，其作用尚不清楚。因此，我们通过开发D-DT转基因（D-DT Tg）小鼠来探索D-DT在光致癌中的作用，并为未来针对D-DT的研究提供了研究模型。与野生型 (WT) 小鼠相比，慢性 UVB 暴露加速了 D-DT Tg 小鼠的肿瘤发展，并且 D-DT Tg 小鼠中观察到的肿瘤发生率高于 WT 小鼠。在 D-DT Tg 照射的小鼠角质形成细胞中，p53、PUMA 和 Bax 的表达低于 WT 小鼠。这些结果表明 D-DT Tg 过表达可以预防 UVB 诱导的角质形成细胞凋亡。总而言之，这些发现支持 D-DT 作为光致癌作用中功能上重要的细胞因子和预防光致癌作用的潜在治疗靶点。
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.