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

BACKGROUND: 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. METHODS: 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. RESULTS: 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/ß-catenin/Wnt3a pathway. CONCLUSION: CD19 may serve as a common biomarker or therapeutic target of psoriasis and MDD via PPARγ/ß-catenin/Wnt3a pathway.

The Protective Effect of Low Dose of Lipopolysaccharide Pretreatment on Endotoxin-Induced Uveitis in Rats Is Associated with Downregulation of CSF-1 and Upregulation of LRR-1.

PURPOSE: To observe the effect of low dose of lipopolysaccharide (LPS) pretreatment on the expression of CSF-1 and LRR-1 in rats with endotoxin-induced uveitis (EIU), and to explore the possible role of TLR4. METHOD: EIU was induced by a single subcutaneous injection of 200 µg LPS. For the endotoxin tolerance group, the induction of EIU was preceded by a daily subcutaneous injection of 0.1 mg/kg LPS for five days. Clinical scores were graded at 24 h after EIU under a slit lamp microscope. HE stain was performed to observe the histopathology. The concentrations of IL-17, INF-γ, and IL-6 in aqueous humor were quantified with enzyme-linked immunosorbent assay. Real-time PCR, Western blot, and immunofluorescence analysis were used to determine the expression of NF-κB P65 and the activation of CSF-1, LRR-1. RESULTS: : Low dose of LPS pretreatment produced a suppressive effect by significantly reducing the inflammatory reaction of anterior segment as measured by slit lamp and histopathology. It also significantly reduced the concentrations of IL-17, INF-γ, and IL-6 in aqueous humor and the expression of CSF-1 and NF-κB P65, while increased the expression of LRR-1 compared to the EIU group. CONCLUSIONS: Low dose of LPS pretreatment can ameliorate endotoxin-induced uveitis in rats. This protection may be associated with upregulation of LRR-1 and downregulation of CSF-1, which is regulated by TLR4 signaling pathway.