Development of novel therapeutic method for photoaging and photocarcinogenesis by targeting D-DT and MIF

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Toyama
• Principal Investigator: Shimizu Tadamichi 富山大学, 大学院医学薬学研究部(医学), 教授 (70260396)
• Co-Investigator(Kenkyū-buntansha): 牧野 輝彦 富山大学, 大学院医学薬学研究部(医学), 准教授 (90359711)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: D-DT / MIF / 光老化 / 紫外線

Outline of Final Research Achievements

Here, to elucidate the possible role of D-dopachrome tautomerase (D-DT) in photocarcinogenesis, the acute and chronic effects of UVB in the skin were examined using D-DT transgenic (Tg) and wild-type (WT) mice. D-DT Tg mice skin showed higher levels of D-DT protein expression without irradiation. However, following UVB exposure, D-DT protein expression dramatically increased in comparison with that of WT mice. Increased incidence of tumorigenesis was observed in the Tg than WT mice following chronic UVB irradiation. Next, it was also clarified whether the acceleration of photo-induced carcinogenesis in the Tg mice was mediated by the inhibition of apoptosis. The epidermis derived from the D-DT Tg mice showed less substantially decreased levels of p53 after acute UVB exposure in comparison with the WT mice. These results suggest that chronic UVB exposure enhances D-DT production, which may inhibit the p53-dependent apoptotic processes and thereby induce photocarcinogenesis in the skin.

Free Research Field

皮膚科学