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Updated: Aug 6, 2026
Lung microRNA Profiling Across the Estrous Cycle in Ozone-exposed Mice
Published on: January 7, 2019
Identification of distinct gene and miRNA expression profiles in severe early-onset COPD providing novel insights in
Nicolaas Jacobus Bekker1,2, Johannes Ll Van Nijnatten1,2,3, Peter L Horvatovich4
1Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
Objective:
Severe early-onset-chronic obstructive pulmonary disease (SEO-COPD) represents the most severe form of COPD that manifests at an earlier age than common COPD. We hypothesise that this is driven by a partially different disease pathogenesis and investigated whether SEO-COPD has a distinct gene and miRNA expression profile.
Methods:
RNA and small RNA sequencing was performed on lung tissue from 18 SEO-COPD, 22 common COPD and 32 non-COPD control subjects. Differential gene expression analysis was performed to identify SEO-COPD-specific genes and miRNA signatures. This was followed by gene set enrichment analysis, pathway enrichment, genome-wide association studies catalog interrogation, expression quantitative trait loci (eQTL) analysis, immunohistochemical validation, mRNA-miRNA integration and cellular deconvolution.
Results:
We identified 105 SEO-COPD specific genes and three SEO-COPD specific miRNAs. Pathway analysis showed enrichment of B-cell-mediated adaptive immunity, chemotaxis and extracellular matrix (ECM) pathways among genes upregulated in SEO-COPD, including the B-cell marker CD79A and ECM component FBLN1 as leading-edge genes. More CD79A-positive infiltrates were observed in SEO-COPD lung tissue compared with control. For 15 SEO-COPD genes, COPD- or lung function-associated single nucleotide polymorphisms were identified, while eQTLs were identified for six SEO-COPD-associated genes. mRNA-miRNA integration identified miR331-3p as a potential regulator of the ECM-related gene expression changes in SEO-COPD.
Conclusions:
The identified lung tissue gene and miRNA expression profiles for SEO-COPD support the presence of a distinct pathogenetic phenotype of SEO-COPD characterised by B-cell-mediated immunity, ECM dysregulation as well as genetic pre-disposition.
