CYP1B1, VEGFA, BCL2, and CDKN1A Affect the Development of Chronic Obstructive Pulmonary Disease.

Abstract

Purpose:

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by poor airflow. The purpose of this study was to explore the mechanisms involved in the development of COPD.

Patients and Methods:

The mRNA expression profile GSE100281, consisting of 79 COPD and 16 healthy samples, was acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between COPD samples and healthy samples were analyzed using the limma package. Functional enrichment analysis for the DEGs was carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Furthermore, DEG-compound pairs were predicted using the Comparative Toxicogenomics Database. The KEGG metabolite IDs corresponding to the compounds were also obtained through the MetaboAnalyst pipeline. Based on the diffusion algorithm, the metabolite network was constructed. Finally, the expression levels of key genes were determined using quantitative PCR (qPCR).

Results:

There were 594 DEGs identified between the COPD and healthy samples, including 242 upregulated and 352 downregulated genes. A total of 696 DEG-compound pairs, such as BCL2-C00469 (ethanol) and BCL2-C00389 (quercetin) pairs, were predicted. CYP1B1, VEGFA, BCL2, and CDKN1A were included in the top 10 DEG-compound pairs. Additionally, 57 metabolites were obtained. In particular, hsa04750 (inflammatory mediator regulation of TRP channels)-C00469 (ethanol) and hsa04152 (AMPK signaling pathway)-C00389 (quercetin) pairs were found in the metabolite network. The results of qPCR showed that the expression of CYP1B1, VEGFA, BCL2, and CDKN1A was consistent with that predicted using bioinformatic analysis.

Conclusion:

CYP1B1, VEGFA, BCL2, and CDKN1A may play important functions in the development and progression of COPD.

• Authors: Danlei Yang, Ying Yan, Fen Hu, Tao Wang
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 15 Pg. 167-175 ( 2020) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 32158203 (Publication Type: Journal Article)
• Copyright: © 2020 Yang et al.

Chemical References

• BCL2 protein, human
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Proto-Oncogene Proteins c-bcl-2
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• CYP1B1 protein, human
• Cytochrome P-450 CYP1B1

Topics

• Case-Control Studies
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Cytochrome P-450 CYP1B1 (genetics, metabolism)
• Databases, Genetic
• Disease Progression
• Gene Expression Profiling
• Gene Regulatory Networks
• Humans
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Pulmonary Disease, Chronic Obstructive (diagnosis, genetics, metabolism)
• Signal Transduction (genetics)
• Transcriptome
• Vascular Endothelial Growth Factor A (genetics, metabolism)