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Volume 27, Issue 18
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work.

Objective

The objective of the study was to analyze and validate potential therapeutic targets and biomarkers in THP-1 cells that were exposed to MSU.

Methods

THP-1 cells were exposed to MSU. The inflammatory effect was characterized, and RNA-Seq analysis was then carried out. The differential genes obtained by RNA-Seq were analyzed with gene expression omnibus (GEO) series 160170 (GSE160170) gout-related clinical samples in the GEO database and gout-related genes in the GeneCards database. From the three analysis approaches, the genes with significant differences were verified by the differential genes’ transcription levels. The interaction relationship of long non-coding RNA (lncRNA) was proposed by ceRNA network analysis.

Results

MSU significantly promoted the release of IL-1β and IL-18 in THP-1 cells, which aggravated their inflammatory effect. Through RNA-Seq, 698 differential genes were obtained, including 606 differential mRNA and 92 differential `LncRNA. Cross-analysis of the RNA-Seq differential genes, the GSE160170 differential genes, and the gout-related genes in GeneCards revealed a total of 17 genes coexisting in the tripartite data. Furthermore, seven differential genes—C-X-C motif chemokine ligand 8 (CXCL8), C-X-C motif chemokine ligand 2 (CXCL2), tumor necrosis factor (TNF), C-C motif chemokine ligand 3 (CCL3), suppressor of cytokine signaling 3 (SOCS3), oncostatin M (OSM), and MIR22 host gene (MIR22HG)—were verified as key genes that analyzed the weight of genes in pathways, the enrichment of inflammation-related pathways, and protein-protein interaction (PPI) nodes combined with the expression of genes in RNA-Seq and GSE160170. It is suggested that MIR22HG may regulate OSM and SOCS3 through microRNA 4271 (miR-4271), OSM, and SOCS3m; CCL3 through microRNA 149-3p (miR-149-3p); and CXCL2 through microRNA 4652-3p (miR-4652-3p).

Conclusion

The potential of CXCL8, CXCL2, TNF, CCL3, SOCS3, and OSM as gout biomarkers and MIR22HG as a therapeutic target for gout are proposed, which provide new insights into the mechanisms of gout biomarkers and therapeutic methods.

© 2024 Bentham Science Publishers
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Transcriptomic Analysis of THP-1 Cells Exposed by Monosodium Urate Reveals Key Genes Involved in Gout
Comb Chem High Throughput Screen 27, 2741 (2024); https://doi.org/10.2174/0113862073262471231011043339
/content/journals/cchts/10.2174/0113862073262471231011043339
/content/journals/cchts/10.2174/0113862073262471231011043339
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  • Article Type:     Research Article
Keyword(s): biomarker; competitive endogenous RNA; Gouty arthritis; monosodium urate; protein-protein interaction; transcriptomic analysis

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