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

Yiran Chen; Zhan Zhang; Ying Zhang; Jingsi Jiang; Yue Luo; Xiaoya Fei; Yi Ru; Bin Li; Huiping Zhang; Taiyi Liu; Yingyao Yang; Le Kuai; Jiankun Song; Ying Luo

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

Am J Transl Res. 2023 Jan 15;15(1):422-434. eCollection 2023.

Authors

Yiran Chen^{1

2}, Zhan Zhang^{1

2}, Ying Zhang^{1

2}, Jingsi Jiang³, Yue Luo³, Xiaoya Fei³, Yi Ru^{1

2}, Bin Li^{1

2

3}, Huiping Zhang⁴, Taiyi Liu⁴, Yingyao Yang^{1

2}, Le Kuai^{1

2}, Jiankun Song³, Ying Luo^{1

2}

Affiliations

¹ Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine Shanghai 200437, China.
² Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine Shanghai 201203, China.
³ Shanghai Skin Disease Hospital, School of Medicine, Tongji University Shanghai 200443, China.
⁴ Shanghai Applied Protein Technology Co., Ltd. 58 Yuanmei Road, Shanghai 200233, China.

PMID: 36777818
PMCID: PMC9908442

Abstract

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.

Keywords: Chinese herbs; Psoriasis; Taodan granules; Wnt signaling pathway; gene set enrichment analysis; ingenuity pathway analysis.