ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1624327
Diphenyl pyridine intervention improves S. aureus-induced pneumonia by globally regulating transcriptome profile
Provisionally accepted
- 1Shihezi University Affiliated Hospital of Traditional Chinese Medicine, Shihezi, China
- 2First Affiliated Hospital of Shihezi University, Shihezi, China
- 3Shihezi University School of Medicine, Shihezi, China
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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.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.We identified 2225 up and 1257 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.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.
Keywords: DP, Pneumonia, RNA-Seq, Hub genes, immune and inflammatory response
Received: 08 May 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Duan, ZHU, Ci, Zhang, Tian, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Duan, Shihezi University Affiliated Hospital of Traditional Chinese Medicine, Shihezi, China
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