Snail regulation in fibroblast-like synoviocytes by a histone deacetylase or glycogen synthase kinase inhibitor affects cell proliferation and gene expression

Background Snail has been linked to the pathogenesis of rheumatoid arthritis (RA). We plan to investigate the regulation of Snail in response to TNF-alpha, histone acetylation, and glycogen synthase kinase-3 (GSK)-3 inhibition in fibroblast-like synoviocytes (FLSs). Methods FLSs from rats with collagen-induced arthritis (CIA) were collected and treated with TNF-alpha alone or a combination with trichostatin A (TSA), a pan-histone deacetylase inhibitor and lithium chloride (LiCl), a glycogen synthase kinase-3 (GSK)-3 inhibitor. Results We demonstrated for the first time that nuclear expression of Snail in FLSs from rats with CIA was correlated with the levels of extracellular TNF-alpha and acetylation status. Cell proliferation and viability of CIA FLSs were reduced in response to TSA treatment and short-hairpin RNA specific to Snail. LiCl treatment increased Snail and cadherin-11 (Cad-11) expression in CIA FLSs. Conclusion We suggested from this study that targeting TNF-alpha-histone deacetylase-Snail signaling axis or the Wnt signaling pathway in FLSs might provide therapeutic interventions for the treatment of RA in the future.

Automated summary

The study demonstrated the correlation between nuclear expression of Snail in CIA FLSs from rats with the levels of extracellular TNF-alpha and acetylation status. Intervention targeting the TNF-alpha-histone deacetylase-Snail signaling axis or the Wnt signaling pathway in FLSs may offer new therapeutic opportunities for treating RA. The inhibitory effects on cell proliferation and viability of CIA FLSs were observed with TSA treatment and specific RNA interference targeting Snail, while LiCl treatment increased Snail and Cadherin-11 expression in CIA FLSs.