靛玉红可能通过靶向MAPK14参与银屑病的发病  

Indirubin may be involved in the pathogenesis of psoriasis by targeting MAPK14

作　　者：刘守刚 刘芳华 陈永锋 LIU Shougang;LIU Fanghua;CHEN Yongfeng(Dermatology Hospital,Southern Medical University,Guangzhou 510091,China;Guangdong Provincial People′s Hospital Ganzhou Hospital,Ganzhou 341099,China)

机构地区：[1]南方医科大学皮肤病医院,广东广州510091 [2]广东省人民医院赣州医院,江西赣州341099

出　　处：《皮肤性病诊疗学杂志》2024年第6期381-390,共10页Journal of Diagnosis and Therapy on Dermato-venereology

基　　金：广东省中医药局科研项目(20202130)。

摘　　要：目的探讨靛玉红在银屑病中的作用靶点,初步阐明靛玉红在银屑病中可能通过MAPK14对银屑病产生的影响。方法从高通量基因表达(GEO)数据库下载GSE30999和GSE78097银屑病数据集,分别作为训练集和验证集。筛选出差异表达基因,然后分析其生物学功能和通路。与靛玉红靶点基因取交集获取差异表达的靛玉红靶点基因,分析基因的相关性和验证基因差异表达情况。采用LASSO回归模型和Cox回归模型筛选靛玉红的最佳靶点基因,与靛玉红进行分子对接分析两者之间的结构关系。结果在GSE30999数据集中,共发现8个靛玉红靶点基因,与对照组相比,均有差异表达。其中7个基因均具有较高的诊断价值(AUC均>0.8),1个基因具有较低诊断价值(AUC>0.6)。GO和KEGG富集分析显示靛玉红的8个靶点基因主要与细胞衰老、化学致癌-受体激活、脂质与动脉粥样硬化、急性髓系白血病和AGE-RAGE信号通路在糖尿病并发症中的作用有关。通过LASSO回归模型和Cox回归模型筛选了靛玉红的最佳靶点基因——MAPK14基因。分子对接显示靛玉红与MAPK14紧密结合。结论靛玉红可能通过MAPK14参与银屑病发病机制的调控和治疗。Objective To investigate the target of indirubin in psoriasis,and to elucidate the possible effect of indirubin on psoriasis through MAPK14.Methods The GSE30999 and GSE78097 psoriasis datasets downloaded from the Gene Expression Omnibus(GEO)database were used as training and validation sets,respectively.The differentially expressed genes were screened,and their biological functions and pathways were analyzed.Intersections with indirubin target genes were used to obtain differentially expressed indirubin target genes.Meanwhile gene correlation was analyzed and differential gene expression was verified.LASSO and Cox regression model were used to screen the best target genes for indirubin.Molecular docking of indirubin was performed to analyze the structural relationship.Results A total of 8 indirubin target genes were found in the GSE30999 dataset,which were differentially expressed compared with the control group.Seven genes had high diagnostic value(AUC>0.8),and one gene had low diagnostic value(AUC>0.6).GO and KEGG enrichment analyses showed that the eight indirubin target genes were mainly related to cell aging,chemical carcinogenic receptor activation,lipid and atherosclerosis,acute myeloid leukemia,and AGE-RAGE signaling pathways in diabetic complications.The best target gene of indirubin,MAPK14 gene,was screened by LASSO and Cox regression model.Molecular docking suggested that indirubin was tightly bound to MAPK14.Conclusion Indirubin may be involved in the regulation of the pathogenesis and treatment of psoriasis through MAPK14.

关 键 词：银屑病 靛玉红 MAPK14 高通量基因表达 

分 类 号：R275[医药卫生—中医皮科]