Identification of Small Airway Epithelium-Related Hub Genes in Chronic Obstructive Pulmonary Disease
Lanlan Lin1,2, Guofu Lin1,2, Xiaohui Chen1,2
1Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China.
Background:
Pulmonary small airway epithelia are the primary site of cellular and histological alterations in chronic obstructive pulmonary disease (COPD), while the potential therapeutic hub genes of pulmonary epithelia are rarely identified to elucidate profound alterations in the progression of the disease.
Methods:
Microarray dataset of GSE11906 containing small airway epithelia from 34 healthy non-smokers and 33 COPD patients was applied to screen differentially expressed genes (DEGs). Weighted gene correlation network analysis (WGCNA) was further used to identify the hub genes related to clinical features. Moreover, single-cell RNA sequencing data from GSE173896 and GSE167295 dataset were applied to explore the expression and distribution of the hub genes. The expression levels of hub genes in epithelial cells stimulated by cigarette smoke extract (CSE) were detected by RT-qPCR.
Results:
Ninety-eight DEGs correlated with clinical features of COPD were identified via limma and WGCNA. Eight hub genes (including AKR1C3, ALDH3A1, AKR1C1, CYP1A1, GPX2, CBR3, AKR1B1 and GSR) that might exert an antioxidant role in COPD process were identified. Single-cell transcriptomic analysis indicated that the expressions of AKRAC3, ALDH3A1, GPX2, CBR3 and AKR1B1 were significantly increased in the COPD group when compared with the normal group. Moreover, we found that the expression of ALDH3A1 was the most abundantly expressed in ciliated cells. RT-qPCR results indicated that the majority of candidate novel genes were significantly elevated when the epithelial cells were exposed to CSE.
Conclusion:
Through integrating limma, WGCNA, and protein-protein interaction (PPI) analysis, a total of eight candidate hub genes of pulmonary airway epithelia were identified in COPD. Moreover, single-cell transcriptomic analysis indicated that ALDH3A1 was enriched in ciliated cells, which may provide a new insight into the pathogenesis and treatment of COPD.
Insights
Researchers identified eight key genes in pulmonary airway epithelia linked to chronic obstructive pulmonary disease (COPD). These genes, potentially involved in antioxidant roles, offer new therapeutic targets for COPD treatment.
Area of Science:
- Pulmonary Medicine
- Genetics
- Molecular Biology
Background:
- Pulmonary small airway epithelia undergo significant changes in chronic obstructive pulmonary disease (COPD).
- Identifying therapeutic hub genes in airway epithelia is crucial for understanding COPD progression.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and hub genes in pulmonary small airway epithelia of COPD patients.
- To explore the expression and distribution of identified hub genes using single-cell RNA sequencing.
- To validate the expression of hub genes in epithelial cells exposed to cigarette smoke extract (CSE).
Main Methods:
- Analysis of microarray data (GSE11906) to identify DEGs.
- Weighted gene correlation network analysis (WGCNA) to identify clinical feature-related hub genes.
- Single-cell RNA sequencing (GSE173896, GSE167295) for gene expression and distribution analysis.
- RT-qPCR to detect gene expression in CSE-stimulated epithelial cells.
Main Results:
- Ninety-eight DEGs correlated with COPD clinical features were identified.
- Eight hub genes (e.g., AKR1C3, ALDH3A1, GPX2) with potential antioxidant roles in COPD were identified.
- Single-cell analysis revealed increased expression of AKRAC3, ALDH3A1, GPX2, CBR3, and AKR1B1 in COPD patients, with ALDH3A1 enriched in ciliated cells.
- RT-qPCR confirmed elevated expression of most candidate genes upon CSE stimulation.
Conclusions:
- Eight candidate hub genes in pulmonary airway epithelia were identified in COPD through integrated analysis.
- ALDH3A1 enrichment in ciliated cells provides novel insights into COPD pathogenesis.
- These identified hub genes represent potential therapeutic targets for COPD.
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