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. 2023 Jan 13:16:183-196.
doi: 10.2147/JIR.S388934. eCollection 2023.

Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis

Qianqian Zhao #  1 , Yongliang Tang #  2 , Luyu Zhang  1 , Na Sun  3 , Qiling Liu  3 , Rongqiang Zhang  3
Affiliations

Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis

Qianqian Zhao et al. J Inflamm Res. .

Abstract

Purpose: In order to further study the biological functions of glutathione peroxidases (GPXs) and their expression level in patients with osteoarthritis (OA), we fully explored the potential relationship between GPXs and OA. This will provide new ideas for basic biological studies and therapeutic strategies for OA patients.

Patients and methods: In this study, bioinformatics techniques were used to explore the biological functions of five GPXs. The core genes related to the biological functions of GPXs were identified by constructing a protein-protein interaction network (PPI). In addition, we utilized microarray data in public databases to analyze the expression levels of GPXs in OA patients and healthy controls. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of GPXs in OA patients and controls to validate our bioinformatic analysis results.

Results: Enrichment analysis showed GPXs were mainly enriched in the glutathione metabolic pathway and participate in the biological process of oxidative stress response, and further play an antioxidant role. The PPI network indicated that superoxide dismutase 1 (SOD1), superoxide dismutase 2(SOD2) and catalase (CAT) were the core proteins of this network. GPX1 was regulated by the greatest number of miRNAs. Experiments showed that the expression of GPX1 was elevated in OA patients compared with controls.

Conclusion: GPXs play an important antioxidant role in oxidative stress response. The expression of GPX1 was elevated in peripheral blood mononuclear cells (PBMCs) of OA patients. The changes of GPXs in OA patients may regulate the level of oxidative stress, which may influence synovial lesions and chondrocyte apoptosis.

Keywords: biological functions; glutathione peroxidase; osteoarthritis.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
A flow chart illustrating the analysis process of this study.
Figure 2
Figure 2
GO and KEGG pathway enrichment analysis of GPXs. (A) GO terms for GPXs enrichment analysis. The X-axis represents gene proportions, and the Y-axis represents enrichment terms. The three shapes of circle, triangle and square represent BP, CC and MF, respectively. The size of the shapes shows the level of enrichment. (B) KEGG pathway for GPXs enrichment analysis. The X-axis represents gene proportions, and the Y-axis represents enrichment terms. Circles represent the KEGG pathway. The size of the shape shows the level of enrichment.
Figure 3
Figure 3
PPI network analysis of GPXs. Pink rhombuses represent GPXs and purple ovals represent interacting genes.
Figure 4
Figure 4
GPXs-miRNA interaction network. Red rhombuses represent GPXs. Navy blue ovals represent miRNA. Light blue ovals represent predicted proteins that co-regulate with miRNA.
Figure 5
Figure 5
Regulation of GPXs by TFs. Pink rhombuses represent GPXs and purple ovals represent interacting TFs.
Figure 6
Figure 6
The results of microarray-based meta-analysis. (A) Forest plot of GPX1 expression between OA group and control group. (B) Forest plot of GPX2 expression between OA group and control group. (C) Forest plot of GPX3 expression between OA group and control group. (D) Forest plot of GPX4 expression between OA group and control group. (E) Forest plot of GPX6 expression between OA group and control group.
Figure 7
Figure 7
Evaluating GPXs expression in OA patients using qRT-PCR. (A) Relative expressions of GPX1 in OA patients and controls. (B) Relative expressions of GPX4 in OA patients and controls. *p < 0.05.
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