| Title |
Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha1-antitrypsin deficiency
|
|---|---|
| Published in |
International Journal of Chronic Obstructive Pulmonary Disease, November 2017
|
| DOI | 10.2147/copd.s145445 |
| Pubmed ID | |
| Authors |
Cristina Esquinas, Sabina Janciauskiene, Ricardo Gonzalo, Gemma Mas de Xaxars, Beata Olejnicka, Irene Belmonte, Miriam Barrecheguren, Esther Rodriguez, Alexa Nuñez, Francisco Rodriguez-Frias, Marc Miravitlles |
| Abstract |
COPD has complex etiologies involving both genetic and environmental determinants. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors. Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD. Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity. Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study. We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. We also integrated the miRNA and the differentially expressed putative target mRNA. For data analyses, we used the R statistical language R Studio (version 3.2.5). The severe and mild COPD-AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy. In severe COPD-AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD-AATD disease. Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients. Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD-AATD. Nonetheless, our findings warrant further validation in large studies. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 18% |
| Student > Ph. D. Student | 4 | 11% |
| Student > Bachelor | 4 | 11% |
| Student > Doctoral Student | 2 | 5% |
| Other | 2 | 5% |
| Other | 5 | 13% |
| Unknown | 14 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 18% |
| Biochemistry, Genetics and Molecular Biology | 4 | 11% |
| Agricultural and Biological Sciences | 2 | 5% |
| Immunology and Microbiology | 2 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 7 | 18% |
| Unknown | 15 | 39% |
Attention Score in Context
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All research outputs
#20,663,600
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Outputs from International Journal of Chronic Obstructive Pulmonary Disease
#2,079
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#264,227
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Outputs of similar age from International Journal of Chronic Obstructive Pulmonary Disease
#60
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