Open AccessSnail regulation in fibroblast-like synoviocytes by a histone deacetylase or glycogen synthase kinase inhibitor affects cell proliferation and gene expression
Author(s) -
Po-Chuan Shen,
Po-Chun Chang,
Jeng-Long Hsieh
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0257839
Subject(s) - trichostatin a , histone deacetylase , gsk 3 , gsk3b , snail , wnt signaling pathway , glycogen synthase , histone deacetylase 2 , biology , signal transduction , histone deacetylase inhibitor , cancer research , chemistry , histone , microbiology and biotechnology , biochemistry , phosphorylation , ecology , gene
Background Snail has been linked to the pathogenesis of rheumatoid arthritis (RA). We plan to investigate the regulation of Snail in response to TNF-α, 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-α 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-α 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-α-histone deacetylase-Snail signaling axis or the Wnt signaling pathway in FLSs might provide therapeutic interventions for the treatment of RA in the future.