NAMPT可能通过烟酸代谢途径参与银屑病的发病

The role of NAMPT in the pathogenesis of psoriasis may be through the regulation of niacin metabolic pathway

目的探讨烟酰胺磷酸核糖转移酶(NAMPT)在银屑病中的作用机制,初步阐明NAMPT在银屑病中对烟酰胺腺嘌呤二核苷酸(NAD^(+))代谢途径的影响。方法从人类自噬基因数据库和GEO数据库下载线粒体自噬基因和银屑病微阵列数据集,筛选线粒体自噬差异表达基因(DEGs)。通过差异表达和接受者操作特征曲线(ROC)分析进行验证和评估。利用LASSO和COX回归模型筛选特征基因。利用皮尔逊分析方法和基因富集分析(GSEA)分别研究基因相关性和功能分析。结果共鉴定出16个银屑病线粒体自噬DEGs,在银屑病中均高表达且具有较高的诊断价值。鉴定出的DEGs主要与NOD样受体信号通路、自噬-动物、甲型流感、化学致癌-受体激活和脂质与动脉粥样硬化通路有关。NAMPT被确定为银屑病的特征基因,主要与蛋白酶体、嘧啶代谢、泛素介导的蛋白水解、DNA复制、抗原处理和呈递、氨酰基tRNA生物合成、细胞质DNA传感途径、卵母细胞减数分裂、同源重组和TOLL样受体信号通路有关。在银屑病中,NAD^(+)代谢途径被激活,与NAMPT呈正相关。在NAD^(+)代谢途径中BST1低表达,与NAMPT呈负相关;PARP9和PNP高表达,与NAMPT呈正相关。结论NAMPT在银屑病中呈高表达,NAD^(+)代谢途径处于激活状态,二者呈正相关。NAMPT可能在NAD^(+)代谢途径中通过BST1、PARP9和PNP调控银屑病的发病。

Objective To investigate the mechanisms of nicotinamide phosphoribosyl transferase(NAMPT)in the pathogenesis of psoriasis and to elucidate the effect of NAMPT on the nicotinamide adenine dinucleotide(NAD^(+))metabolic pathway in psoriasis.Methods Mitophagy gene and psoriasis microarray datasets were downloaded from the human autophagy gene database and GEO database to screen differentially expressed genes(DEGs)of mitophagy.Validation and assessment were performed by differential expression and receiver operating characteristic(ROC)curve analysis.LASSO and COX regression models were used to screen signature genes.Gene correlation and functional analysis were performed using Pearson and gene enrichment analysis(GSEA).Results A total of 16 differentially expressed mitophagy genes were identified in psoriasis,which all were highly expressed in psoriasis with high diagnostic value.The DEGs of mitophagy were mainly associated with NOD-like receptor signaling pathway,autophagy-animal,influenza A,chemo carcinogenic-receptor activation and lipid/atherosclerotic pathways.NAMPT was identified as a signature gene of psoriasis,mainly associated with the proteasome,pyrimidine metabolism,ubiquitin-mediated proteolysis,DNA replication,antigen processing and presentation,aminoacyl tRNA biosynthesis,cytoplasmic DNA sensing pathway,oocyte meiosis,homologous recombination and TOLL-like receptor signaling pathway.In psoriasis,NAD metabolic pathways were activated and positively correlated with NAMPT.In the NAD^(+)metabolic pathway,expression levels of BST1 were low and negatively correlated with NAMPT.In contrast,expression levels of PARP9 and PNP were high and positively correlated with NAMPT.Conclusions In psoriasis,NAMPT is highly expressed and NAD^(+)metabolic pathway is activated.Expression levels of NAMPT are positively correlated with the activity of NAD^(+)metabolic pathway.NAMPT may be involved in the pathogenesis of psoriasis through BST1,PARP9 and PNP in the NAD^(+)metabolic pathway.