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

PLoS One. 2021 Sep 28;16(9):e0257839. doi: 10.1371/journal.pone.0257839. eCollection 2021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Lithium Chloride / pharmacology*
  • Rats
  • Snail Family Transcription Factors / metabolism*
  • Synoviocytes / cytology*
  • Synoviocytes / drug effects
  • Synoviocytes / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Hydroxamic Acids
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Tumor Necrosis Factor-alpha
  • trichostatin A
  • Lithium Chloride

Grants and funding

Hsieh (108-2314-B-273-005-MY3, Ministry of Science and Technology, Taiwan) Chang (ANHRF107-8, An Nan Hospital, China Medical University, Tainan, Taiwan) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.