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Published on: August 7, 2017
Exploratory analysis of the key role of immune function changes in BPD
Tianyi Wu1,2,3,4, Xingmeng Fu1,2,3,4, Xiaoxia Gong1,2,3,4
1Department of Respiratory Children's Hospital of Chongqing Medical University Chongqing China.
Insights
This study identifies four key genes (Cd3e, Cd3g, Cd247, Itk) and the T cell receptor signaling pathway as crucial in bronchopulmonary dysplasia (BPD). Their downregulation impairs immune function and worsens lung inflammation in premature infants.
Area of Science:
- Neonatal Medicine
- Pulmonology
- Immunology
Background:
- Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease affecting premature infants.
- Understanding the molecular mechanisms underlying BPD is critical for developing effective treatments.
Purpose of the Study:
- To identify key genes and signaling pathways associated with BPD through transcriptomic analysis.
- To validate these findings in both human patient data and an animal model.
Main Methods:
- Transcriptomic analysis of Gene Expression Omnibus (GEO) dataset (GSE32472) from infants with and without BPD.
- Bioinformatic analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction, and Gene Set Enrichment Analysis (GSEA).
- Transcriptome sequencing and quantitative polymerase chain reaction (qPCR) validation in a hyperoxia-induced rat model of BPD.
Main Results:
- Four hub genes (Cd3e, Cd3g, Cd247, Itk) and the T cell receptor signaling pathway were identified as significantly associated with BPD.
- Downregulation of these genes and pathway was observed in BPD patients and the animal model.
- Reduced T cell receptor signaling function correlates with immune dysfunction, increased lung inflammation, and susceptibility to infections in BPD.
Conclusions:
- The identified genes and T cell receptor signaling pathway play a critical role in the pathogenesis of BPD.
- Targeting these pathways may offer therapeutic strategies to mitigate BPD severity and associated complications.
Abstract:
Bronchopulmonary dysplasia (BPD) is one of the most prevalent and severe chronic lung diseases in premature infants. The objective of the current study was to screen for key BPD-associated genes and pathways by transcriptomic analysis from clinical patients and animal models. In our study, the differentially expressed genes were screened from 58 children with 14-day BPD and 40 normal children in the GSE32472 dataset of the Gene Expression Omnibus database. Then, we identified four hub genes (Cd3e, Cd3g, Cd247, and Itk) and a signaling pathway (T cell receptor signaling pathway) by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction analysis. The differential expression of the relevant pathways and gene sets among the groups was verified via GSEA analysis. Subsequently, a rat model of BPD with hyperoxia-induced lung injury was established, and the transcriptome sequencing of the whole lung tissue was performed. A similar analysis was done on the sequencing data of the hub genes and associated pathway screening to verify the accuracy. Ultimately, quantitative polymerase chain reaction was performed to validate the transcriptomics data of core gene expression in the rat model. Our study revealed that the downregulation of the expression of the above four key genes in the course of BPD leads to a decrease in the function of T cell receptor signaling pathways, it causes immune dysfunction and increases the severity of lung inflammation as well as susceptibility to other respiratory infectious diseases.
