光老化对皮肤角质形成细胞中转录组学相关基因表达的影响

Effect of Photoaging on Transcriptomic-Related Gene Expression in Skin Keratinocytes

目的探讨皮肤光老化的关键基因和相关通路,为阐明皮肤光老化的分子机制提供科学依据。方法UVB照射构建原代人角质形成细胞光老化模型,采用RNA-seq筛选差异表达基因,进行GO和KEGG富集分析。选取部分差异基因进行qRT-PCR验证。结果UVB照射可引起原代人角质形成细胞形态变化,细胞活力下降,衰老相关β-半乳糖苷酶阳性细胞率增加。RNA-Seq转录组学分析共发现1468个差异表达基因(DEGs),其中681个上调基因,787个下调基因。GO富集分析到差异表达基因参与炎症、氧化损伤、角化等生物学过程。KEGG富集筛选到16条与光老化有关的通路包括细胞外基质(ECM)-受体相互作用、p53信号通路等。多种胶原蛋白以及氧化损伤和炎症相关基因都发生了改变。结论UVB照射能诱导原代人角质形成细胞衰老,同时诱发细胞的转录组学发生显著变化,差异基因涉及多个信号转导通路,为深入探讨皮肤光老化提供了新的方向。

Objective To explore the key genes and related pathways of skin photoaging,and to provide scientific basis for elucidating the molecular mechanism of skin photoaging.Methods The photoaging model of primary human keratinocytes was established by UVB irradiation,and the differentially expressed genes(DEGs)were screened by RNA-seq,and GO and KEGG enrichment were analyzed.Some differential genes were selected for further verification by qPCR.Results UVB irradiation induced morphological changes of primary keratinocytes,decreased cell viability,and increased the rate of age-relatedβ-galactosidase positive cells.A total of 1468 DEGs were identified by RNA-Seq transcriptome analysis,including 681 up-regulated genes and 787 down-regulated genes.GO enrichment to differentially expressed genes involved in inflammation,oxidative damage,keratosis and other biological processes.KEGG enrichment analysis screened 16 pathways related to photoaging,including ECM-receptor interaction and p53 signaling pathway.A variety of collagen proteins were altered,as were genes associated with oxidative damage and inflammation.Conclusion UVB irradiation can induce senescence of primary human keratinocytes.Moreover,the transcriptome of genes inducing primary keratinocytes changes significantly,and the differential genes involve multiple signal transduction pathways,and their mechanisms need to be further explored.