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Abstract
Ultraviolet (UV) irradiation is an environmental factor that causes skin aging, and is also a major factor leading to cumulative alterations of skin structure, function and appearance. To investigate the effects of Selenium (Sel) on UV-induced skin aging, hairless mice were treated for 4 weeks with UV irradiation and topical application of Sel. Then, the effects of Sel were measured in the skin of these mice via histological analysis and Western blotting. According to the results of wrinkle formation analysis, the topical application of Sel induced a reduction in wrinkling formation in the damaged skin of the UV-irradiated mice. Additionally, our histological analysis demonstrated that the skin thickness in the Sel-treated group was less than in the UV-irradiated group. Furthermore, in an effort to investigate the mechanisms underlying the effects of Sel, the expression levels of matrix-metalloproteinase (MMP) and MAPK protein were assessed in both groups. The application of Sel induced a reduction in MMP-1 expression levels to the levels observed in the non-irradiated group. However, the expression level of MMP-9 was increased slightly in the Sel application group as compared with the vehicle application group. Additionally, the levels of ERK phosphorylation were increased by the application of Sel, but the levels of JNK and p38 were not altered by Sel treatment. These results suggest the possibility that Sel should be considered as a skin aging-protective and therapeutic drug candidate, which functions via the regulation of MMP expression levels.
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Figure 1.
Schematic diagram of the irradiation site in the dorsal skin surface of hairless mice (A) and the irradiation schedule lead to induce skin aging (B). The UV dose was increased weekly by 1 MED up to 4 MED. Vehicle or Selenium was applied to the backs of hairless mice after UV irradiation.
Figure 2.
Inhibition of UV-induced wrinkle formation by Sel in the hairless mice. Wrinkle formation was measured by replica grading at final week. The level of wrinkle were assessed according to the scoring system suggested by Bissette et al. (1990) (grad 0: no wrinkles, grade 1: a few shallow wrinkles, grade 2: some wrinkles, grade 3: several deep wrinkles). The values of data represented mean±SD of three experiments. ∗P<0.05 is the significance level compared to the control (No irradiation) group, P<0.05 is the significance level compared to the vehicle applicated group.
Figure 3.
Inhibition of UV-induced skin thickness by Sel in hairless mice. The dorsal skin of hairless mice was prepared into histological slide and skin thickness were measured the wide from epidermis to dermis. Cellular morphology was viewed at 20x magnification and the values of data represented mean±SD of three experiments. ∗P<0.05 is the significance level compared to the control (No irradiation) group, P<0.05 is the significance level compared to the vehicle applicated group.
Figure 4.
Effect of Selenium (Sel) on UV-induced MMP expression using Western blot (A) and immunohistochemical staining (B). Total cell lysate were prepared from skin tissues of control, UV-irradiation, UV/Vehicle and UV/Sel group, as described in Materials and Methods. Fifty micrograms of protein per sample were immunoblotted with antibodies for each protein. Three samples were assayed in triplicate using Western blotting. The values are the mean±SD. ∗P<0.05 is the significance level compared to the control (No irradiation) group, ∗∗P<0.05 is the significance level compared to the vehicle applicated group.
Figure 5.
Effect of selenium (Sel) on UV-induced MAPK protein expression using Western blot. Total cell lysate were prepared from skin tissues of control, UV-irradiation, UV/Vehicle and UV/ Sel group, as described in Materials and Methods. Fifty micrograms of protein per sample were immunoblotted with antibodies for each protein. Three samples were assayed in triplicate using Western blotting. The values are the mean±SD. ∗P<0.05 is the significance level compared to the control (No irradiation) group, ∗∗P<0.05 is the significance level compared to the vehicle applicated group.
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