2026-04-17T05:52:25Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1240842025-12-05T15:55:48Zcom_2072_1057col_2072_478860col_2072_478917

00925njm 22002777a 4500 dc Esquinas López, Cristina author Janciauskiene, Sabina author Gonzalo, Ricardo author Mas de Xaxars Giner, Gemma author Olejnicka, Beata author Belmonte, Irene author Barrecheguren, Miriam author Rodríguez, Esther author Nuñez, Alexa author Rodríguez-Frías, Francisco author Miravitlles Fernández, Marc author 2018-08-02T08:17:27Z 2018-08-02T08:17:27Z 2017-11-29 2018-08-02T08:17:27Z 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. Malalties pulmonars obstructives cròniques Errors congènits del metabolisme Micro RNAs Expressió gènica Chronic obstructive pulmonary diseases Inborn errors of metabolism MicroRNAs Gene expression Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha1-antitrypsin deficiency