Diphenyl pyridine intervention improves S. aureus-induced pneumonia by globally regulating transcriptome profile
Wei Duan1, Qingfeng Zhu2, Hai Ci3
1Clinical Laboratory, Shihezi University Affiliated Hospital of Traditional Chinese Medicine, Shihezi, Xinjiang, China.
Background:
Pneumonia, induced by various bacteria or viruses, is a globally prevalent inflammatory disease that threatens the life of millions of people. Staphylococcus aureus (S. aureus) is a major pathogen of pneumonia and can be inhibited by Diphenyl pyrimidine (DP), while the underlying mechanisms are largely unknown.
Methods:
In this study, we conducted the S. aureus-induced rat pneumonia model and then performed DP treatment to inhibit the injury. Meanwhile, whole transcriptome sequencing (RNA-seq) experiment was performed to identify the dysregulated genes with expression and alternative splicing changes, as well as their enriched functions. Hub genes and immune cell proportion changes by DP were also identified to explore the underlying mechanism.
Results:
We identified 2,225 up and 1,257 down DEGs between DP and SA samples, and found they were significantly enriched in immune and inflammatory response pathways, as well as angiogenesis and apoptosis pathways. At the same time, DP treatment also significantly altered the alternative splicing profile, including 3898 AS genes and 416 co-regulated genes with DEGs. Functional analysis of co-regulated genes demonstrated they were enriched in immune response, signal transduction, and apoptosis regulation pathways. Finally, we identified ten hub genes by protein-protein network analysis from DEGs, including CCNA2, TOP2A, CDK1, ESPL1, KIF2C, PBK, UHRF1, RACGAP1, PCLAF, and RAD51 that were totally repressed by DP treatment.
Conclusion:
In summary, our study demonstrated that DP treatment can profoundly modulate the immune and inflammatory response by regulating the transcriptome profile of peripheral blood monocytes (PBMCs). The identified hub genes by DP treatment are potential therapeutic targets for S. aureus-induced pneumonia in future.
Insights
Diphenyl pyrimidine (DP) treats Staphylococcus aureus pneumonia by altering gene expression and immune responses. This study identifies key genes regulated by DP, offering potential therapeutic targets for bacterial pneumonia.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Pneumonia is a widespread inflammatory disease caused by bacteria or viruses.
- Staphylococcus aureus (S. aureus) is a primary bacterial cause of pneumonia.
- Diphenyl pyrimidine (DP) shows inhibitory effects against S. aureus, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the therapeutic mechanisms of Diphenyl pyrimidine (DP) in Staphylococcus aureus (S. aureus)-induced pneumonia.
- To identify gene expression and alternative splicing changes induced by DP treatment using whole transcriptome sequencing.
- To explore potential therapeutic targets by analyzing hub genes and immune cell proportions.
Main Methods:
- Established an S. aureus-induced rat pneumonia model.
- Administered DP treatment to inhibit pneumonia-induced injury.
- Performed whole transcriptome sequencing (RNA-seq) to analyze gene expression and alternative splicing.
- Conducted protein-protein network analysis to identify hub genes.
Main Results:
- Identified 2,225 upregulated and 1,257 downregulated differentially expressed genes (DEGs) enriched in immune, inflammatory, angiogenesis, and apoptosis pathways.
- Observed significant alterations in alternative splicing, with 3,898 AS genes and 416 co-regulated genes with DEGs.
- Found co-regulated genes enriched in immune response, signal transduction, and apoptosis regulation.
- Identified ten hub genes (CCNA2, TOP2A, CDK1, ESPL1, KIF2C, PBK, UHRF1, RACGAP1, PCLAF, RAD51) repressed by DP.
Conclusions:
- DP treatment modulates immune and inflammatory responses by regulating the transcriptome profile of peripheral blood monocytes (PBMCs).
- The identified hub genes represent potential therapeutic targets for S. aureus-induced pneumonia.
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