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Title: | Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha1-antitrypsin deficiency |
Author: | Esquinas López, Cristina Janciauskiene, Sabina Gonzalo, Ricardo Mas de Xaxars Giner, Gemma Olejnicka, Beata Belmonte, Irene Barrecheguren, Miriam Rodríguez, Esther Nuñez, Alexa Rodríguez-Frías, Francisco Miravitlles Fernández, Marc |
Keywords: | Malalties pulmonars obstructives cròniques Errors congènits del metabolisme Micro RNAs Expressió gènica Chronic obstructive pulmonary diseases Inborn errors of metabolism MicroRNAs Gene expression |
Issue Date: | 29-Nov-2017 |
Publisher: | Dove Medical Press |
Abstract: | Introduction: 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. Materials and methods: 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). Results: 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. Conclusions: 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.2147/COPD.S145445 |
It is part of: | International Journal of Chronic Obstructive Pulmonary Disease, 2017, vol. 12, p. 3381-3390 |
URI: | http://hdl.handle.net/2445/124084 |
Related resource: | https://doi.org/10.2147/COPD.S145445 |
ISSN: | 1176-9106 |
Appears in Collections: | Articles publicats en revistes (Infermeria de Salut Pública, Salut mental i Maternoinfantil) |
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