ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1562244

This article is part of the Research TopicPrevention and Treatment of Skin DiseasesView all 7 articles

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

Provisionally accepted
Jiangming  ZhongJiangming Zhong*Ling  LiangLing LiangNan  ZhaoNan ZhaoJing  WangJing WangPeng  ShuPeng Shu*
  • HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong, China

The final, formatted version of the article will be published soon.

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 RARβ, 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.

Keywords: retinol, Retinyl palmitate, DNA Damage, UVB, Homologous Recombination

Received: 17 Jan 2025; Accepted: 11 Apr 2025.

Copyright: © 2025 Zhong, Liang, Zhao, Wang and Shu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jiangming Zhong, HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong, China
Peng Shu, HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong, China

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