Peripheral Blood Mononuclear Cell Gene Expression in Chronic Obstructive Pulmonary Disease: miRNA and mRNA Regulation

Abstract

Introduction

The mechanisms underlying chronic obstructive pulmonary disease (COPD) remain unclear. Genetic and genomic changes may play a significant role in the pathogenesis of COPD. Identification of differentially expressed genes and miRNAs and their regulatory mechanisms at the whole-genome level will provide a comprehensive understanding of the development of COPD.

Methods

Peripheral blood mononuclear cells (PBMCs) from 12 patients with COPD and 12 normal controls were examined at the miRNA and mRNA expression levels using Affymetrix GeneChip. Microarray data were analyzed with Affymetrix Transcriptome Analysis Console 2.0 and GeneSpring software. Gene interaction pathways of the differentially expressed genes and miRNA-mRNA regulation were analyzed using the Ingenuity Pathway Analysis software. Four differentially expressed genes and one miRNA were further confirmed using RT-qPCR.

Results

One hundred and thirty-three upregulated and 973 downregulated genes were identified in PBMCs of patients with COPD. Pathway analysis on the differentially expressed genes in COPD revealed significant enrichment in IL-8 signaling and iCOS-iCOSL signaling in T helper cells. Seventy-seven upregulated miRNAs and 43 downregulated miRNAs were differentially expressed between PBMCs from patients with COPD and normal controls. Among these 120 differentially expressed miRNAs, 42 miRNAs targeting 28 upregulated genes and 69 miRNAs targeting 498 downregulated genes were identified. The expression of CXCR1, HBEGF, TREM-1, and hsa-miR-148a-3p was more elevated in patients with COPD than in normal controls, whereas NFAT5 was decreased.

Conclusion

miRNAs and mRNAs are differentially expressed in PBMCs of patients with COPD, compared with normal controls. miRNAs regulate the expression of mRNAs, and thus play a role in the pathogenesis of COPD. Investigating these relationships may provide further insight into the mechanisms of COPD.

Keywords:

• COPD
• whole-genome transcription
• gene
• miRNA
• peripheral blood mononuclear cells

Ethics Approval and Consent to Participate

The study was approved by the Xiangya Hospital of Central South University Institutional Review Board Committees. Patients provided written informed consent before participation.

Consent for Publication

All patient data were de-identified.

Acknowledgments

The authors thank all staff of the Microarray Core Lab of the Department of Immunology, University of Texas Southwestern Medical Center, for their selfless help.

Disclosure

The authors declare no competing conflicts of interest for this work.

Additional information

Funding

This research was supported by the Freedom Explore Program of Central South University (grant no. 2012QNZT128). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.