Department of Dermatology, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, Hunan, China.
Biochem Genet. 2023 Aug;61(4):1606-1624. doi: 10.1007/s10528-023-10334-8. Epub 2023 Jan 31.
Skin aging is the most intuitive manifestation of aging. Skin aging inevitably leads to cosmetic and psychological problems, and even diseases. The present study aims to research the pathological and molecular mechanisms underlying skin aging and identify the therapeutic agents for reversing skin aging. Two available gene expression datasets (GSE55118 and GSE72264) for skin aging were downloaded from Gene Expression Omnibus, followed by bioinformatic analyses performed on the datasets. Firstly, 169 crucial mRNAs, 27 crucial miRNAs and 50 crucial lncRNAs closely related to skin aging were identified by weighted gene co-expression network analysis. Then, function Enrichment Analysis performed by Metascape database showed that skin aging involves a variety of biological functions, such as detection of stimulus, response to steroid hormone and water channel activity, regulation of muscle contraction. Next, ten hub genes including AQP4, TRPM8, TBR1, NTSR2, MPPED1, BARHL2, PAX9, CPN1, CES3, and CHGB were screened out by the protein-protein interaction analysis. Next, the "lncRNA-miRNA-mRNA" network and the "lncRNA-miRNA-hub mRNA" network were constructed to explore the competing endogenous RNAs mechanism of skin aging. Finally, ten significant potential small molecules mitigating skin aging were screened using CMAP platform, including tretinoin, pifithrin, selamectin, entinostat, bretazenil, syringic-acid, BRD-K96475865, emedastine, abacavir, and rotenone, and their reliability was verified by molecular docking experiments. The present study provided basis for revealing the molecular mechanism of skin aging and identified the potential candidate drugs for mitigating skin aging.
皮肤衰老最直观的表现就是衰老。皮肤衰老不可避免地会导致美容和心理问题,甚至疾病。本研究旨在研究皮肤衰老的病理和分子机制,并确定逆转皮肤衰老的治疗药物。从基因表达综合数据库(GEO)中下载了两个可用于皮肤衰老的基因表达数据集(GSE55118 和 GSE72264),并对这些数据集进行了生物信息学分析。首先,通过加权基因共表达网络分析鉴定了 169 个与皮肤衰老密切相关的关键 mRNAs、27 个关键 miRNAs 和 50 个关键 lncRNAs。然后,Metascape 数据库的功能富集分析显示,皮肤衰老涉及多种生物学功能,如刺激检测、类固醇激素反应和水通道活性、肌肉收缩调节。接下来,通过蛋白质-蛋白质相互作用分析筛选出包括 AQP4、TRPM8、TBR1、NTSR2、MPPED1、BARHL2、PAX9、CPN1、CES3 和 CHGB 在内的 10 个关键基因。接下来,构建了“lncRNA-miRNA-mRNA”网络和“lncRNA-miRNA-关键 mRNA”网络,以探讨皮肤衰老的竞争内源 RNA 机制。最后,使用 CMAP 平台筛选出 10 种具有显著潜力的抗皮肤衰老小分子,包括维甲酸、吡非尼酮、塞拉菌素、恩替诺特、苯二氮䓬、丁香酸、BRD-K96475865、依美斯汀、阿巴卡韦和鱼藤酮,并通过分子对接实验验证了它们的可靠性。本研究为揭示皮肤衰老的分子机制提供了依据,并确定了缓解皮肤衰老的潜在候选药物。