Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha I-antitrypsin deficiency

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MARC

Esquinas, CristinaUniversity of Barcelona,Vall d'Hebron University Hospital (author)

Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha I-antitrypsin deficiency

Article/chapterEnglish2017

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2017
10 s.

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LIBRIS-ID:oai:lup.lub.lu.se:b42f1481-b243-45d9-b0ac-aa1a6c00d6a9
https://lup.lub.lu.se/record/b42f1481-b243-45d9-b0ac-aa1a6c00d6a9URI
https://doi.org/10.2147/COPD.S145445DOI

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Language:English
Summary in:English

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Alpha1-antitrypsin deficiency
COPD
Gene expression
Integrative analysis
miRNAs

Added entries (persons, corporate bodies, meetings, titles ...)

Janciauskiene, SabinaHannover Medical School (author)
Gonzalo, RicardoVall d'Hebron University Hospital (author)
de Xaxars, Gemma MasVall d'Hebron University Hospital (author)
Olejnicka, BeataLund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups(Swepub:lu)lung-bol (author)
Belmonte, IreneVall d'Hebron University Hospital (author)
Barrecheguren, MiriamVall d'Hebron University Hospital (author)
Rodriguez, EstherVall d'Hebron University Hospital (author)
Nuñez, AlexaVall d'Hebron University Hospital (author)
Rodriguez-Frias, FranciscoVall d'Hebron University Hospital (author)
Miravitlles, MarcVall d'Hebron University Hospital (author)
University of BarcelonaVall d'Hebron University Hospital (creator_code:org_t)

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In:International Journal of COPD12, s. 3381-33901176-9106

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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