TCN1 as an inflammatory regulator in psoriasis: Activation of the NF-κB pathway and potential therapeutic target

Abstract

Objective

This study investigates how TCN1 regulates inflammation and the cell cycle in psoriasis, focusing on the NF-κB pathway through in vitro experiments and bioinformatics analyses.

Methods

DEGs were identified by analyzing transcriptome data from four datasets comparing psoriatic lesions and normal skin (GSE34248, GSE30999, GSE14905, and GSE13355). Validation of TCN1 expression following biologic treatment was conducted using GSE201827, GSE51440, and GSE117239. GO and GSEA were performed to explore biological pathways.

The expression levels of TCN1 in psoriatic lesions and healthy skin were assessed by qPCR and immunohistochemistry (IHC). In vitro, HaCaT keratinocytes were stimulated with TNF-α and IL-17 A, and TCN1 expression was modulated through siRNA-mediated knockdown and plasmid-mediated overexpression. Subsequent changes in TCN1 and key inflammatory cytokines were evaluated by qPCR and Western blotting (WB). Furthermore, immunofluorescence assays were performed to visualize the subcellular localization of TCN1 and the nuclear translocation of phosphorylated p65 (p-p65) in HaCaT cells. Cell cycle progression was assessed using BrdU-PI flow cytometry.

Results

TCN1 was upregulated in psoriatic lesions, and its expression levels were positively correlated with the PASI score. Following biologic treatment, TCN1 expression was reduced. TCN1 overexpression was associated with activation of the NF-κB signaling pathway, accompanied by increased synthesis of psoriasis-related inflammatory mediators, as well as an elevated proportion of cells in the S phase of the cell cycle.

Conclusions

TCN1 is essential in modulating inflammation and the cell cycle in psoriasis, implying its value as both a biomarker for diagnosis and a candidate for therapeutic intervention.