Mining of key genes based on transcriptome sequencing and WGCNA analysis for the treatment of psoriasis vulgaris with compound Zeqi granules

OBJECTIVE: To identify the key target genes for the treatment of psoriasis vulgaris by compound Zeqi granules based on transcriptome sequencing and weighted gene co-expression network analysis. Methods: 15 BALB/c mice were randomly divided into normal group, model group and ZQ group at 29.25 g/kg. Imiquimod was used to establish an psoriasis vulgaris model, and samples were taken after 28 d of continuous gavage of ZQ granules after successful modeling. Total RNA was extracted from the samples of each group and then transcriptome sequencing was carried out, and differential analysis was performed by using DESeq2 package in R. The WGCNA package performs weighted gene co-expression network analysis to identify the key target genes for the treatment of psoriasis vulgaris. The WGCNA package performed weighted gene co-expression analysis. Fluorescence quantitative polymerase chain reaction was performed to validate the key core genes. Meanwhile, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the core genes in the co-expression module.RESULTS:Compared with the model group, the erythema and scaling of the skin lesions in the dorsal modeling area of the mice in the ZQ group were significantly reduced, the degree of infiltration was significantly reduced, the PASI score was significantly reduced (P < 0.01), and the degree of histopathological damage of the skin was significantly reduced. Transcriptome sequencing difference analysis showed that 270 genes were significantly changed in the ZQ group compared with the model group, and a total of 9 co-expression modules were obtained by WGCNA analysis, and the module with the highest correlation with both the model group and the ZQ group, the M yellow module, which contained 1527 genes, was selected as the key module (P < 0.05). Intersecting the relevant differential genes obtained above with the genes of the modules obtained from WGCNA that were strongly correlated with the model group and the ZQ group finally yielded 45 candidate genes. Protein Interaction Network analysis was performed on the 45 candidate genes to obtain the key core genes: Ndufb1, Rplp2, Atp5e, Ndufa2, Atp5k. Real-time PCR validation of the key core genes was consistent with the sequencing results. GO analysis and KEGG enrichment analysis of the genes in the key modules revealed that the key core genes were mainly related to the participation in the extension step of protein synthesis and oxidative phosphorylation process.CONCLUSION:Compound Zeqi granules may treat psoriasis vulgaris by targeting Ndufb1, Rplp2, Atp5e, Ndufa2, and Atp5k, which are involved in protein synthesis elongation steps, oxidative phosphorylation-related metabolic pathways.