PTPRC Knockdown Inhibits Inflammation in Gouty Arthritis by Blocking the JAK2/STAT3 Signaling Pathway

Abstract

Gouty arthritis (GA) is a prevalent inflammatory arthropathy triggered by the deposition of monosodium uric acid (MSU) crystals. However, the molecular mechanism underlying GA pathogenesis is still unclear. GA-related differentially expressed genes (DEGs) were identified from the GSE242872 and GSE190138 datasets. A rat model of GA was established by injecting MSU crystals. The lipopolysaccharide (LPS) and MSU-stimulated THP-1 cells were used for In Vitro studies. The severity of GA was assessed by joint swelling, dysfunction, and hematoxylin and eosin staining. Inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay. The downstream target of protein tyrosine phosphatase receptor type C (PTPRC) was explored by bioinformatics analysis and western blot. Four key genes, including IL 6, PTPRC, CXCL1, and CCR7, were overexpressed in GA. PTPRC knockdown attenuated GA, accompanied by reduced joint swelling, dysfunction index, and inflammatory cell infiltration in GA rats. The levels of pro-inflammatory cytokines were lowered after PTPRC knockdown. Bioinformatics analysis demonstrated a significant relationship between PTPRC and the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways and PTPRC knockdown reduced the phosphorylation levels of the JAK2 and STAT3 in vivo and In Vitro. Treatment with CA1, an activator of the JAK2/STAT3 pathway, significantly counteracted the effects of PTPRC knockdown on GA. PTPRC knockdown attenuates inflammation in GA by suppressing the JAK2/STAT3 pathway, which provides a new insight into the treatment of GA.