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Identification of potential gene targets in systemic vasculitis using DNA microarray analysis
Yiwen Feng1, Miao Zheng1, Shujie Gan1
1Vascular Surgery Department, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, P.R. China.
Abstract:
The present study aimed to identify the involvement of critical genes in systemic vasculitis, to gain an improved understanding of the molecular circuity and to investigate novel potential gene targets for systemic vasculitis treatment. The dual‑color cDNA microarray data of GSE16945, consisting of peripheral mononuclear blood cell specimens from 13 patients with systemic vasculitis and 16 healthy controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened in systemic vasculitis compared with controls using BRB ArrayTools, followed by the construction of a protein‑protein interaction (PPI) network using the clusterProfiler package, and significant functional interaction (FI) module selection. Furthermore, transcriptional factors (TFs) among the identified DEGs were predicted and a transcriptional regulation network was constructed. A total of 173 up- and 93 downregulated genes were identified, which were mainly associated with immune response pathways. FBJ murine osteosarcoma viral oncogene homolog (FOS), ubiquitin B (UBB), signal transducer and activator of transcription 1 (STAT1) and MX dynamin‑like GTPase 1 (MX1) were identified as hub proteins in the PPI network. Furthermore, UBB, FOS, and STAT1 were hub proteins in the three identified FI modules, respectively. In total, nine TFs were predicted among the DEGs. Of the DEGs that were predicted to be TFs, STAT1, v‑maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) and tyrosine 3‑monooxygenase/tryptophan 5‑monooxygenase activation protein Z (YWHAZ), which interacted with each other, were identified to regulate further DEGs as target genes. Various genes, including FOS, UBB, MX1, STAT1, MAFB, and YWHAZ may be potential targets useful for the treatment of systemic vasculitis.
Insights
This study identified key genes involved in systemic vasculitis, revealing potential new treatment targets. Key genes like FOS, UBB, STAT1, and MX1 were highlighted for their roles in immune responses.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Systemic vasculitis involves complex molecular pathways.
- Identifying critical genes is crucial for understanding disease mechanisms and developing treatments.
Purpose of the Study:
- To identify critical genes in systemic vasculitis.
- To understand the molecular circuitry of the disease.
- To investigate novel gene targets for systemic vasculitis treatment.
Main Methods:
- Downloaded and analyzed dual-color cDNA microarray data (GSE16945) from patients with systemic vasculitis and healthy controls.
- Screened for differentially expressed genes (DEGs) using BRB ArrayTools.
- Constructed protein-protein interaction (PPI) and transcriptional regulatory networks.
Main Results:
- Identified 173 upregulated and 93 downregulated genes, primarily associated with immune response pathways.
- FBJ murine osteosarcoma viral oncogene homolog (FOS), ubiquitin B (UBB), signal transducer and activator of transcription 1 (STAT1), and MX dynamin-like GTPase 1 (MX1) were identified as hub proteins.
- STAT1, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein Z (YWHAZ) were identified as key transcriptional factors regulating DEGs.
Conclusions:
- Genes including FOS, UBB, MX1, STAT1, MAFB, and YWHAZ represent potential therapeutic targets for systemic vasculitis.
- Understanding these gene networks offers insights into systemic vasculitis pathogenesis.
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