Department of Dermatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Biomed Res Int. 2020 Jun 29;2020:5842795. doi: 10.1155/2020/5842795. eCollection 2020.
Acne is the eighth most common disease worldwide. Disease burden of acne such as anxiety, reduced self-esteem, and facial scarring lowers the life quality of acne patients. Isotretinoin is the most potent treatment for moderate-severe acne. However, the adverse events of isotretinoin especially teratogenicity limit its use. This study aims at investigating the therapeutical mechanisms of isotretinoin using bioinformatics analysis. Differentially expressed genes (DEGs) were filtered from microarray datasets GSE10432, GSE10433, and GSE11792. Functional and pathway enrichment analyses of DEGs were performed. Protein-protein interaction (PPI) network and module analyses were also conducted based on DEGs. Using isotretinoin for 1 week, , , and were upregulated and might mediate sebocytes apoptosis and thus decreased sebum production; originated from activated TNF signaling pathway and could be related with "acne-flare". While treating with isotretinoin for 8 weeks, key genes were downregulated, including , , , , , and , which may be associated with decreased sebum synthesis; , , and also probably associated with apoptosis of sebocytes. There were only two common genes including and which worked in both 1 week and 8 weeks and could associate with decreased sebum synthesis and apoptosis of sebocytes, respectively. These results indicate potential therapeutics and side effect mechanisms of isotretinoin in the acne treatment and provide a research direction to further investigate the therapeutic mechanism of isotretinoin and thus develop retinoid-like compounds with similar curative effect and without teratogenicity.
痤疮是全球第八大常见疾病。痤疮的疾病负担，如焦虑、自尊心降低和面部疤痕，降低了痤疮患者的生活质量。异维 A 酸是治疗中重度痤疮最有效的药物。然而，异维 A 酸的不良反应，特别是致畸性，限制了它的使用。本研究旨在通过生物信息学分析研究异维 A 酸的治疗机制。从微阵列数据集 GSE10432、GSE10433 和 GSE11792 中筛选差异表达基因（DEGs）。对 DEGs 进行功能和通路富集分析。还基于 DEGs 进行蛋白质-蛋白质相互作用（PPI）网络和模块分析。用异维 A 酸治疗 1 周后，、、和上调，可能介导皮脂腺细胞凋亡，从而减少皮脂生成；起源于激活的 TNF 信号通路，可能与“痤疮发作”有关。用异维 A 酸治疗 8 周后，关键基因下调，包括、、、、、和，可能与皮脂合成减少有关；、和可能与皮脂腺细胞凋亡有关。只有两个共同基因，包括和，在 1 周和 8 周都起作用，分别与减少皮脂合成和皮脂腺细胞凋亡有关。这些结果表明异维 A 酸在痤疮治疗中的潜在治疗和副作用机制，并为进一步研究异维 A 酸的治疗机制提供了研究方向，从而开发出具有类似疗效且无致畸性的类视黄醇化合物。
