Gene set enrichment analysis and ingenuity pathway analysis to verify the impact of Wnt signaling in psoriasis treated with Taodan granules

Background: Taodan granules (TDGs), traditional Chinese herbals, have effectiveness in relieving skin erythema, scales, and other symptoms of psoriasis. Yet mechanisms of TDGs remain indistinct.

Objective: To indicate the molecular mechanisms of TDGs in treating psoriasis.

Materials and methods: Primarily, transcriptional profiling was applied to identify differentially expressed genes (DEGs), proceeding with Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analysis were used for functional enrichment analysis. Subsequently, levels of selected genes were validated by RT-PCR and western blotting.

Results: The GSEA results revealed TDGs could down-regulate the Wnt signaling pathway to ameliorate skin lesions of imiquimod (IMQ)-induced psoriatic models mice. IPA core network associated with Wnt signaling pathways in TDGs for psoriasis was established. Thereinto zeste homolog 2 (EZH2), CTNNB1, tumor protein p63 (TP63), and WD repeat domain 5 (WDR5) were considered as upstream genes in the Wnt signaling pathway. Experimental verification indicated TDGs could down-regulate EZH2, CTNNB1, and WDR5 at the mRNA and protein levels, along with up-regulate TP63 levels. Moreover, TDGs were confirmed to reduce RAC2 and WNT5A at mRNA and protein levels of the Wnt signaling pathway.

Conclusions: TDGs may improve psoriasis through the regulation for upstream genes (down-regulating levels of EZH2, CTNNB1, and WDR5; up-regulating TP63 levels) of Wnt signaling pathway, thus reducing levels of RAC2 and WNT5A in the Wnt signaling pathway.