Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis
Background. Notwithstanding the mounting evidence to suggest that systemic lupus erythematosus (SLE) accelerates the progression of atherosclerosis, the mechanisms underlying this phenomenon are yet to be completely understood. This research examined the molecular mechanism behind this vascular comp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2023-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2023/4508436 |
| _version_ | 1797647592358674432 |
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| author | Han Zhang Yinde Huang Xin Li Wenbin Chen Yu Lun Jian Zhang |
| author_facet | Han Zhang Yinde Huang Xin Li Wenbin Chen Yu Lun Jian Zhang |
| author_sort | Han Zhang |
| collection | DOAJ |
| description | Background. Notwithstanding the mounting evidence to suggest that systemic lupus erythematosus (SLE) accelerates the progression of atherosclerosis, the mechanisms underlying this phenomenon are yet to be completely understood. This research examined the molecular mechanism behind this vascular complication. Methods. The Gene Expression Omnibus database was retrieved to acquire the gene expression datasets for SLE (GSE109248) and atherosclerosis (GSE100927). The shared differentially expressed genes (DEGs) of SLE and atherosclerosis were screened with the help of the “limma” package in R software, followed by function enrichment analysis, protein–protein interaction (PPI) network construction, key module analysis, hub gene selection, and coexpression analysis. Results. In GSE109248 and GSE100927, 1195 and 418 DEGs in totals were identified, respectively. Subsequently, we acquired 78 common DEGs (70 upregulated genes and eight downregulated genes) with the same expression trends by using the Venn diagram. Finally, 12 hub genes, including PTPRC, TYROBP, FCGR3A, ITGAX, LCP2, IL1B, IRF8, LILRB2, CD68, C1QB, CCR7, and C1QA were identified by using seven different algorithms in Cytohubba. The functional analysis illustrates that these genes were predominantly enriched in immune and inflammation response, lipid and atherosclerosis, and osteoporosis. These results indicate an important role of SLE in inducing excessive inflammation, which may be medicate by these hub genes and can induce osteoporosis and imbalance of the normal mineral balance in the body as well as lipid abnormalities, which eventually leads to premature onset of atherosclerosis. In total, nine transcription factors (TFs) that may participate in regulating the function of these genes were identified. All hub genes and four TFs were validated successfully. Conclusion. The results of our research show that SLE and atherosclerosis have common DEGs, pathophysiology, and hub genes. These findings can provide fresh evidence and insights into a further investigation into the mechanisms at play. |
| first_indexed | 2024-03-11T15:19:44Z |
| format | Article |
| id | doaj.art-03807381e77e4f08980c0c9c962d1298 |
| institution | Directory Open Access Journal |
| issn | 1466-1861 |
| language | English |
| last_indexed | 2024-03-11T15:19:44Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj.art-03807381e77e4f08980c0c9c962d12982023-10-29T00:00:03ZengHindawi LimitedMediators of Inflammation1466-18612023-01-01202310.1155/2023/4508436Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset AtherosclerosisHan Zhang0Yinde Huang1Xin Li2Wenbin Chen3Yu Lun4Jian Zhang5Department of Vascular and Thyroid SurgeryDepartment of Vascular and Thyroid SurgeryDepartment of Vascular and Thyroid SurgeryDepartment of Vascular and Thyroid SurgeryDepartment of Vascular and Thyroid SurgeryDepartment of Vascular and Thyroid SurgeryBackground. Notwithstanding the mounting evidence to suggest that systemic lupus erythematosus (SLE) accelerates the progression of atherosclerosis, the mechanisms underlying this phenomenon are yet to be completely understood. This research examined the molecular mechanism behind this vascular complication. Methods. The Gene Expression Omnibus database was retrieved to acquire the gene expression datasets for SLE (GSE109248) and atherosclerosis (GSE100927). The shared differentially expressed genes (DEGs) of SLE and atherosclerosis were screened with the help of the “limma” package in R software, followed by function enrichment analysis, protein–protein interaction (PPI) network construction, key module analysis, hub gene selection, and coexpression analysis. Results. In GSE109248 and GSE100927, 1195 and 418 DEGs in totals were identified, respectively. Subsequently, we acquired 78 common DEGs (70 upregulated genes and eight downregulated genes) with the same expression trends by using the Venn diagram. Finally, 12 hub genes, including PTPRC, TYROBP, FCGR3A, ITGAX, LCP2, IL1B, IRF8, LILRB2, CD68, C1QB, CCR7, and C1QA were identified by using seven different algorithms in Cytohubba. The functional analysis illustrates that these genes were predominantly enriched in immune and inflammation response, lipid and atherosclerosis, and osteoporosis. These results indicate an important role of SLE in inducing excessive inflammation, which may be medicate by these hub genes and can induce osteoporosis and imbalance of the normal mineral balance in the body as well as lipid abnormalities, which eventually leads to premature onset of atherosclerosis. In total, nine transcription factors (TFs) that may participate in regulating the function of these genes were identified. All hub genes and four TFs were validated successfully. Conclusion. The results of our research show that SLE and atherosclerosis have common DEGs, pathophysiology, and hub genes. These findings can provide fresh evidence and insights into a further investigation into the mechanisms at play.http://dx.doi.org/10.1155/2023/4508436 |
| spellingShingle | Han Zhang Yinde Huang Xin Li Wenbin Chen Yu Lun Jian Zhang Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis Mediators of Inflammation |
| title | Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis |
| title_full | Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis |
| title_fullStr | Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis |
| title_full_unstemmed | Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis |
| title_short | Exploration of Hub Genes and Pathogenetic Pathways in Systemic Lupus Erythematosus Complicated with Early Onset Atherosclerosis |
| title_sort | exploration of hub genes and pathogenetic pathways in systemic lupus erythematosus complicated with early onset atherosclerosis |
| url | http://dx.doi.org/10.1155/2023/4508436 |
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