Ursolic Acid As a Protective Agent Against UVB-Induced Metabolic and Epigenetic Alterations in Human Skin Keratinocytes: An Omics-Based Study

Overview

Journal Cancer Prev Res (Phila)

Specialty Oncology

Date 2024 Dec 24

PMID 39718470

Authors

Shanyi Li

Zixin Li

Hsiao-Chen Dina Kuo

Ah-Ng Kong

Affiliations

Soon will be listed here.

Abstract

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.

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