Role of SNF5 in rheumatoid arthritis by upregulation of p16 and inactivation of JNK pathway

Authors : SHUPENG WU, JING WANG, FANG LI

Pages : 535-542

View : 12 | Download : 5

Publication Date : 2017-12-01

Article Type : Research Paper

Abstract :This study aims to explore the role and the possible underlying molecular mechanism of SNF5 in the pathogenesis of rheumatoid arthritis insert ignore into journalissuearticles values(RA);. MH7A cells were respectively transfected with pc-SNF5 insert ignore into journalissuearticles values(pcDNA3.1 containing the Brg1 coding sequence);, short hairpin RNA against SNF5 insert ignore into journalissuearticles values(shSNF5);, and their negative controls insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(FLSs); obtained from a rat model with adjuvant-induced arthritis. Results showed that the expression of SNF5 was increased in the pc-SNF5 group insert ignore into journalissuearticles values(P < 0.05); while it was decreased in the shSNF5 group insert ignore into journalissuearticles values(P < 0.05);. Afterwards, cell viability after transfection was reduced by SNF5 overexpression insert ignore into journalissuearticles values(P < 0.05, P < 0.01, or P < 0.001);, whereas it was enhanced by SNF5 knockdown insert ignore into journalissuearticles values(P < 0.05 or P < 0.001);. In terms of apoptosis, SNF5 overexpression promoted cell apoptosis insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(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.
Keywords : SNF5, SWItch sucrose nonfermentable, rheumatoid arthritis, p16, JNK pathway