Exploration of common molecular mechanisms of psoriatic arthritis and aging based on integrated bioinformatics and single-cell RNA-seq analysis

Abstract

Objective

This study investigated the key genes shared between Psoriatic arthritis (PSA) and aging.

Methods

By integrating and analyzing single-cell RNA sequencing data from the synovial fluid of PsA patients, peripheral blood of senescent patients, and the normal population, the subpopulation of cells that were jointly upregulated in both was obtained as the core cellular subpopulation. We analyzed the proposed chronology of this core cellular subpopulations and the function of cellular communication, screened the differentially expressed genes in the core cellular subpopulations compared with other categories, analyzed the causal relationship between the differentially expressed genes and PsA by Mendelian randomization and analyzed the enriched pathways of key genes.

Results

T cell subsets were represented in a significant proportion of both PsA and senescent patients, in which CD8-CM was expressed up-regulated in both PsA and senescent populations, and a total of 98 differentially expressed genes were obtained, and a Mendelian randomization study revealed that TGFBR3, PPP3CC, and APOBEC3G were causally associated with PsA. Colocalization analysis was performed to identify co-localized association signals in the PsA GWAS results and expression quantitative trait Loci (eQTL) dataset of key genes, and metabolic pathways that were predominantly enriched for key genes were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG).

Conclusions

In this study, we found that CD8-CM expression was up-regulated in PsA and senescent populations, and identified key genes for PsA and senescence: TGFBR3, PPP3CC and APOBEC3G. This provides new insights into the pathogenesis and combined treatment of PsA and aging.