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

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 expre...

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Bibliographic Details
Published in:PloS one 2020-07, Vol.15 (7), p.e0233814
Main Authors: Xinqiang, Song, Erqin, Dai, Yu, Zhang, Hongtao, Du, Lei, Wang, Ningning, Yang
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Arthritis
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - genetics
Arthritis, Rheumatoid - pathology
Biology and Life Sciences
Care and treatment
Cells, Cultured
Chinese herbal medicine
Chromatography, Liquid
Extracellular matrix
Fibroblasts
Gene expression
Gene Expression Regulation - drug effects
Gene Ontology
Gene sequencing
Genes
Genomes
Health aspects
High-Throughput Nucleotide Sequencing
Humans
Medicine and Health Sciences
Models, Molecular
Molecular docking
Molecular Docking Simulation
Oxidative stress
Oxygen
Peptides
Plant extracts
Proteins
Proteomics
Proteomics - methods
Research and Analysis Methods
Rheumatoid arthritis
Ribonucleic acid
RNA
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Scientific imaging
Spectrometry, Mass, Electrospray Ionization
Synoviocytes
Synoviocytes - drug effects
Synoviocytes - metabolism
Tandem Mass Spectrometry
Testing
Thunder god vine
Transcriptome - drug effects
Triterpenes - pharmacology
Triterpenes - therapeutic use
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0233814