Potential mechanisms of action of celastrol against rheumatoid arthritis: Transcriptomic and proteomic analysis

PLoS One. 2020 Jul 29;15(7):e0233814. doi: 10.1371/journal.pone.0233814. eCollection 2020.

Abstract

The clinical efficacy for treating of celastrol rheumatoid arthritis (RA) has been well-documented, but its mechanism of action remains unclear. Here we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. In this paper, expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / pathology
  • Cells, Cultured
  • Chromatography, Liquid
  • Gene Expression Regulation / drug effects*
  • Gene Ontology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation
  • Pentacyclic Triterpenes
  • Proteomics / methods*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Spectrometry, Mass, Electrospray Ionization
  • Synoviocytes / drug effects
  • Synoviocytes / metabolism
  • Tandem Mass Spectrometry
  • Transcriptome / drug effects*
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Pentacyclic Triterpenes
  • RNA, Messenger
  • Triterpenes
  • celastrol

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant no. U1804179), the Henan Science and Technology Innovation Team, the Investigation on Plant Resources in Dabie Mountains and the Study and Utilization of Active Components of Special plants (grant no. 2017083), Henan key scientific and technological projects (202102310190) and the Nanhu Scholars Program for Young Scholars of Xinyang Normal University (grant no. 2018001).