Role of SNF5 in rheumatoid arthritis by upregulation ofp16 and inactivation of JNK pathway

Abstract

This study aims to explore the role and the possible underlying molecular mechanism of SNF5 in the pathogenesis of rheumatoid arthritis (RA). MH7A cells were respectively transfected with pc-SNF5 (pcDNA3.1 containing the Brg1 coding sequence), short hairpin RNA against SNF5 (shSNF5), and their negative controls (pcDNA3.1 and shNC). The alterations of SNF5 expression were assessed by qRT-PCR and western blot analysis. MTT assay, flow cytometry, and western blot analysis were performed to evaluate proliferation, apoptosis, and expression levels of p16 and JNK pathway associated proteins, respectively. Finally, the effect of SNF5 was verified in fibroblast-like synoviocytes (FLSs) obtained from a rat model with adjuvant-induced arthritis. Results showed that the expression of SNF5 was increased in the pc-SNF5 group (P < 0.05) while it was decreased in the shSNF5 group (P < 0.05). Afterwards, cell viability after transfection was reduced by SNF5 overexpression (P < 0.05, P < 0.01, or P < 0.001), whereas it was enhanced by SNF5 knockdown (P < 0.05 or P < 0.001). In terms of apoptosis, SNF5 overexpression promoted cell apoptosis (P < 0.01). The western blot analysis showed that the phosphorylated levels of proteins involved in the JNK pathway were downregulated by SNF5 overexpression while they were upregulated by SNF5 knockdown (P < 0.05, P < 0.01, or P < 0.001). However, the effect of SNF5 on the expression of p16 was the opposite. Finally, the effect of SNF5 was validated in murine FLSs. In conclusion, SNF5 suppresses proliferation and induces apoptosis of fibroblast-like cells through overexpression of p16 and suppression of the JNK pathway.