Weighted Gene Co-Expression Network Analysis of Oxymatrine in Psoriasis Treatment

J Inflamm Res. 2023 Mar 7:16:845-859. doi: 10.2147/JIR.S402535. eCollection 2023.

Abstract

Purpose: Psoriasis is a common, chronic, inflammatory, recurrent, immune-mediated skin disease. Oxymatrine is effective for treating moderate and severe psoriasis. Here, transcriptional changes in skin lesions before and after oxymatrine treatment of patients with psoriasis were identified using full-length transcriptome analysis and then compared with those of normal skin tissues.

Patients and methods: Co-expression modules were constructed by combining the psoriasis area and severity index (PASI) score with weighted gene co-expression network analysis to explore the action mechanism of oxymatrine in improving clinical PASI. The expression of selected genes was verified using immunohistochemistry, quantitative real-time PCR, and Western blotting.

Results: Kyoto Encyclopedia of Gene and Genome pathway analysis revealed that oxymatrine treatment reversed the abnormal pathways, with an improvement in lesions and a reduction in PASI scores. Gene Ontology (GO) analysis revealed that oxymatrine treatment led to altered GO terms being regulated with a decrease in the PASI score in patients. Therefore, oxymatrine treatment may improve the skin barrier, differentiation of keratinocytes, and alleviate abnormality of organelles such as desmosomes. Protein-protein interaction network interaction analysis revealed that the top five hub genes among many interrelated genes were CNFN, S100A8, SPRR2A, SPRR2D, and SPRR2E, associated with the epidermal differentiation complex (EDC). EDC regulates keratinocyte differentiation. This result indicates that oxymatrine treatment can restore keratinocyte differentiation by regulating the expression of EDC-related genes.

Conclusion: Oxymatrine can improve erythema, scales, and other clinical symptoms of patients with psoriasis by regulating EDC-related genes and multiple pathways, thereby promoting the repair of epithelial tissue and maintaining the dynamic balance of skin keratosis.

Keywords: enrichment analysis; epidermal differentiation complex; epithelial tissue; homeostasis.

Grants and funding

This study was supported by the Natural Science Foundation (82060572) and the Construction of the Talent Platform Project of Ningxia (Innovation Team for Skin Disease Diagnosis and Treatment Technology & Drug Discovery and Development) (No. NXKJT2019012).