(P01-002-23) Effect of Dehydrogenase/Reductase SDR Family Member 9 (DHRS9) on Skin Responses to Acute Ultraviolet Light B Exposure in Mice

Objectives: A previous study found that topically inhibiting retinoic acid (RA) synthesis following acute ultraviolet light B (UVB) led to greater epidermal damage. This study was performed to determine the mechanism of action by which RA may contribute to epidermal recovery following acute exposure of mouse dorsal skin to UVB.

Methods: Dehydrogenase/reductase SDR family member 9 (Dhrs9)^+/- heterozygous C57BL/6 mice were bred for 3 successive generations onto the AIN-93G diet containing the recommended 4IU vitamin A /g diet. Mice remained on the AIN93G diet throughout the experiment. Seven-week-old female and male Dhrs9^-/- null and littermate wild type mice were depilated on the back to synchronize the hair cycle. Five days later, mice were exposed once or not to one minimal erythema dose of UVB (2240 J/m²). Five days post depilation is when RA levels are predicted to peak in the hair cycle. Animals were euthanized by CO₂ asphyxiation 48 hours after UVB irradiation and dorsal skin was collected under yellow light and snap-frozen in liquid nitrogen for retinol and RA quantification by liquid chromatography tandem mass spectrometric (LC/MS/MS) or placed in RNA later. Real time-quantitative polymerase chain reaction (RT-QPCR) was performed on inflammatory markers tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1 β), IL-6, and IL-33. The retinol dehydrogenase Sdr16c5, involved in retinal synthesis in the skin, was also assessed by RT-QPCR.

Results: UVB exposure increased IL-1β(p = 0.016) and decreased IL-6 (p = 0.018). There were no significant differences in TNF-α, IL-33, and Sdr16c5. Retinol and RA were greater in females than males (p < 0.001). UVB reduced retinol (p = 0.002) and RA (p = 0.021) in females only. There were no effects of genotype on any measurement

Conclusions: There is a sex difference in retinol and RA responses to acute UVB exposure in C57BL/6 mouse dorsal skin. Sdr16c5 neither increased following acute UVB nor compensated for lack of Dhrs9. Loss of function of Dhrs9 did not alter the expression of the cytokines tested.

Funding Sources: Texas Woman’s University (TWU) Research Enhancement Program Award #3429 to HBE. TWU Graduate Experiential Student Scholars Program award and the Moore-Khourie Award from the Department of Nutrition and Food Sciences to E-NA.