Identification of CD19 as a shared biomarker via PPARγ/β-catenin/Wnt3a pathway linking psoriasis and major depressive disorder.

Psoriasis, a chronic inflammatory skin disorder, is frequently linked with metabolic, cardiovascular, and psychological comorbidities. Recent research has highlighted the correlation between psoriasis and major depressive disorder (MDD); however, the underlying mechanism remains unclear. Commonly differentially expressed genes (DEGs) in psoriasis and MDD were identified and visualized using data from the GEO database. Subsequently, functional enrichment analysis was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Genemania. The hub gene was selected through LASSO and Random Forest algorithms, validated in clinical tissues using Student's t -test and Receiver Operating Characteristic curve. To investigate the hub gene's function in disease phenotype, we established imiquimod (IMQ)-induced psoriasiform dermatitis and chronic unpredictable mild stress (CUMS) mouse models. Lentiviral shRNA interference was topically applied in mice, and downstream pathways were validated at the mRNA and protein levels. A total of 395 overlapping DEGs were identified from GSE121212 and GSE54568 datasets, and twenty core genes were extracted. Functional enrichment analysis revealed that the core genes were significantly associated with the Wnt signaling pathway, neurodegeneration, and energy metabolism. CD19 was identified as the hub gene through algorithms, and external validation showed remarkable AUC values of 0.69 and 0.74, respectively. The level of CD19 increased significantly in IMQ-treated and CUMS-treated mice. Suppression of CD19 significantly alleviated the phenotypes of IMQ-induced psoriasiform dermatitis and CUMS-induced depressive-like behaviors by regulating the PPARγ/β-catenin/Wnt3a pathway. CD19 may serve as a common biomarker or therapeutic target of psoriasis and MDD via PPARγ/β-catenin/Wnt3a pathway. • Identification of CD19 as a Shared Biomarker linking psoriasis and major depressive disorder. • CD19 could regulate the PPARγ/β-catenin/Wnt3a Pathway pathway. • CD19 could influence the pathogenesis of psoriasis and major depressive disorder. [ABSTRACT FROM AUTHOR]