Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200050, China.
Biomed Res Int. 2017;2017:8717369. doi: 10.1155/2017/8717369. Epub 2017 Oct 24.
RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the transcriptomic level, and many biomarkers have been discovered to be related to the immune response, lipid metabolism, and keratinocyte proliferation. However, few studies have combined analysis from various datasets. In this study, we integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of psoriasis through the analysis of differentially expressed genes (DEGs), pathway analysis, and functional annotation. The revealed biomarkers were further validated through proliferation phenotypes. The results showed that DEGs were functionally related to lipid metabolism and keratinocyte differentiation dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G gene families, as well as pathways that include the PPAR signaling pathway, cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further validated the role that the AKR1B10 gene plays in proliferation. Our study demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing but also its important role in the overproliferation and migration of keratinocyte, which provided evidence for further therapeutic uses for psoriasis.
RNA-seq 技术使我们能够在转录组水平上深入分析银屑病的发病机制,发现了许多与免疫反应、脂质代谢和角质形成细胞增殖相关的生物标志物。然而,很少有研究结合了来自不同数据集的分析。在本研究中,我们整合了不同的银屑病 RNA-seq 数据集,通过差异表达基因(DEGs)分析、通路分析和功能注释来揭示银屑病的发病机制。通过增殖表型进一步验证了所揭示的生物标志物。结果表明,DEGs 与脂质代谢和角质形成细胞分化失调功能相关。结果还显示了新的生物标志物,如 AKR1B10 和 PLA2G 基因家族,以及包括 PPAR 信号通路、细胞因子-细胞因子受体相互作用、α-亚麻酸代谢和糖脂生物合成在内的途径。通过 siRNA 敲低实验,我们进一步验证了 AKR1B10 基因在增殖中的作用。我们的研究不仅证明了 AKR1B10 基因在脂质代谢中的功能障碍,还证明了它在角质形成细胞过度增殖和迁移中的重要作用,为银屑病的进一步治疗提供了证据。