<i>ISG15</i> promotes M5-induced hacat cell proliferation through Wnt signaling in psoriasis

Abstract Objective Psoriasis is a common chronic, recurrent, immune-mediated inflammatory skin disease, which tends to occur in cold areas. Its pathogenesis is currently unclear. This study aims to screen differentially expressed genes in the psoriasis dataset, identify the central genes, detect the expression of central genes in psoriasis lesions of patients in the cold regions and then conduct further research. Methods Differential genes associated with psoriasis in the GEO database were analyzed, and functional enrichment analysis and protein-protein interaction network analysis. The expression results of the identified genes were validated in psoriasis cell models. The ISG15 gene, which showed the most significant difference in expression, was further studied. The expression level of ISG15 protein in psoriasis was examined. Then, we knocked out ISG15 in psoriasis cell models and detected keratinocyte proliferation by MTT, Real-Time PCR and Western Blot. Western Blot showed the expression of β-catenin after ISG15 gene knockout. Results We detected the protein expression of ISG15 in the cold area of Northeast China, and found that the expression of ISG15 increased in patients with psoriasis, and the proliferation of keratinocytes and the expression of β-catenin decreased in psoriasis cell model after ISG15 was knocked down. ISG15 regulates keratinocyte proliferation through Wnt signaling pathway in psoriasis. Conclusions ISG15 expression is increased in psoriatic cells and skin lesions of patients with psoriasis. In psoriasis, ISG15 promotes keratinocyte proliferation through the Wnt signaling pathway.