Synergistic Effects of Retinol and Retinyl Palmitate in Alleviating UVB-Induced DNA Damage and Promoting the Homologous Recombination Repair in Keratinocytes

Ultraviolet B (UVB) rays are a type of ultraviolet radiation emitted by the sun, primarily responsible for skin photodamage. These rays mainly affect the epidermis, leading to direct damage to DNA and contributing to skin cancer development. Retinol and its derivatives are effective in combating skin aging and photodamage, but they often cause skin intolerance, limiting their use despite their potent effects. Therefore, investigating optimal compositions of retinoids is essential to enhance their efficacy against photodamage. In this study, we aimed to investigate the synergistic effects of retinol (ROL) and retinyl palmitate (RPalm) in alleviating UVB-induced DNA damage in human keratinocytes (HaCaT). Applying the ROL+RPalm combination after UVB exposure in HaCaT cells significantly reduced inflammation and apoptosis while promoting collagen synthesis compared to individual treatments with ROL or RPalm. Through bulk mRNA sequencing, we identified that the biological function of the ROL+RPalm synergy is primarily directed toward mediating DNA damage repair. Using comet assays, Western blotting, immunofluorescence, and flow cytometry, we demonstrated the anti-DNA damage effects of ROL+RPalm in HaCaT cells and reconstructed human epidermis. We further elucidated that the molecular mechanism underlying the ROL+RPalm combination involves the activation of RARß, which subsequently triggers the ATM-CHK2-p53 signaling pathway and increases the expression of homologous recombination (HR)-associated repair genes. This combination presents a potential therapeutic strategy for UVB-induced photodamage and emphasizes the synergistic effects of ROL and RPalm in alleviating UVB-induced DNA damage. Overall design: RNA-seq profiling of HaCaT (Human Keratinocyte) cells subjected to UVB irradiation. After UVB irradiation with the addition of ROL or Rpalm or ROL+Rpalm, we wanted to investigate whether ROL or Rpalm or ROL+Rpalm had the ability of anti-photodamage in HaCaT (Human Keratinocyte) cell, especially in DNA repair. Then we performed gene expression profiling analysis using data obtained from RNA seq of 5 different treated ways (control group, UVB treated group, UVB and ROL co-treated group, UVB and Rpalm co-treated group, UVB and ROL with Rpalm co-treated group)in Hacat cell.