Li Shanyi, Li Zixin, Kuo Hsiao-Chen Dina, Kong Ah-Ng
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, PR China.
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, PR China.
Cancer Prev Res (Phila). 2025 Mar 3;18(3):135-144. doi: 10.1158/1940-6207.CAPR-24-0441.
This study aimed to assess how ursolic acid (UA) can protect human skin keratinocytes from damage caused by UVB radiation. Utilizing an omics-based approach, we characterized the features of photodamage and investigated the potential of UA to reverse HaCaT cell subpopulation injury caused by UVB radiation. The most significant changes in metabolite levels after UA treatment were in pathways associated with phosphatidylcholine biosynthesis and arginine and proline metabolism. Treatment with UA can reverse the levels of certain metabolites, including creatinine, creatine phosphate, and succinic acid. Pathways activated by UA treatment in UVB-irradiated HaCaT cells were associated with several biological processes, including the positive regulation of protein modification process, cell division, and enzyme-linked receptor protein signaling pathway. Treatment with UA demonstrates the capability to mitigate the effects of UVB radiation on specific genes, including S100 calcium-binding protein A9 and IL6 receptor. DNA/CpG methylation indicates that UA can partially reverse some of the alterations in the UVB-induced CpG methylome. Utilizing integrated RNA sequencing and methylation sequencing data, starburst plots illustrate the correlation between mRNA expression and CpG methylation status. UA potentially influences the metabolic pathway of glycerophospholipid metabolism by modulating the expression of several key enzymes, including phospholipase A2 group IIA and lipin 2. Altogether, these results indicate that UVB radiation induces metabolic reprogramming, epigenetic changes, and transcriptomic shifts. Meanwhile, UA demonstrates the capacity to inhibit or reduce the severity of these alterations, which may underlie its potential protective role against skin damage caused by UVB exposure. Prevention Relevance: Our research indicates that UA has the potential to mitigate or lessen the impact of UVB radiation, which is known to cause metabolic reprogramming, epigenetic alterations, and transcriptomic changes. These effects could be responsible for UA's possible protective function against skin damage induced by UVB exposure.
本研究旨在评估熊果酸（UA）如何保护人类皮肤角质形成细胞免受紫外线B（UVB）辐射造成的损伤。利用基于组学的方法，我们表征了光损伤的特征，并研究了UA逆转UVB辐射引起的HaCaT细胞亚群损伤的潜力。UA处理后代谢物水平最显著的变化发生在与磷脂酰胆碱生物合成以及精氨酸和脯氨酸代谢相关的途径中。UA处理可逆转某些代谢物的水平，包括肌酐、磷酸肌酸和琥珀酸。在UVB照射的HaCaT细胞中，UA处理激活的途径与几个生物学过程相关，包括蛋白质修饰过程的正调控、细胞分裂和酶联受体蛋白信号通路。UA处理表明其有能力减轻UVB辐射对特定基因的影响，包括S100钙结合蛋白A9和IL6受体。DNA/CpG甲基化表明UA可以部分逆转UVB诱导的CpG甲基化组中的一些改变。利用整合的RNA测序和甲基化测序数据，星爆图说明了mRNA表达与CpG甲基化状态之间的相关性。UA可能通过调节几种关键酶的表达来影响甘油磷脂代谢的代谢途径，这些关键酶包括磷脂酶A2 IIA组和脂素2。总之，这些结果表明UVB辐射会诱导代谢重编程、表观遗传变化和转录组改变。同时，UA显示出抑制或降低这些改变严重程度的能力，这可能是其对UVB暴露引起的皮肤损伤具有潜在保护作用的基础。预防相关性：我们的研究表明，UA有潜力减轻或降低UVB辐射的影响，UVB辐射已知会导致代谢重编程、表观遗传改变和转录组变化。这些影响可能是UA对UVB暴露诱导的皮肤损伤具有可能保护功能的原因。
