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

Esquinas, Cristina; Janciauskiene, Sabina; Gonzalo, Ricardo; de Xaxars, Gemma Mas; Olejnicka, Beata LU ; Belmonte, Irene; Barrecheguren, Miriam; Rodriguez, Esther; Nuñez, Alexa and Rodriguez-Frias, Francisco, et al. (2017) In International Journal of COPD 12. p.3381-3390
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... (More)

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.

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Contribution to journal
publication status
published
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keywords
Alpha1-antitrypsin deficiency, COPD, Gene expression, Integrative analysis, miRNAs
in
International Journal of COPD
volume
12
pages
10 pages
publisher
Dove Press
external identifiers
  • scopus:85037744027
  • wos:000416965400001
ISSN
1176-9106
DOI
10.2147/COPD.S145445
language
English
LU publication?
yes
id
b42f1481-b243-45d9-b0ac-aa1a6c00d6a9
date added to LUP
2018-01-11 13:59:29
date last changed
2018-10-03 10:52:04
@article{b42f1481-b243-45d9-b0ac-aa1a6c00d6a9,
  abstract     = {<p>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.</p>},
  author       = {Esquinas, Cristina and Janciauskiene, Sabina and Gonzalo, Ricardo and de Xaxars, Gemma Mas and Olejnicka, Beata and Belmonte, Irene and Barrecheguren, Miriam and Rodriguez, Esther and Nuñez, Alexa and Rodriguez-Frias, Francisco and Miravitlles, Marc},
  issn         = {1176-9106},
  keyword      = {Alpha1-antitrypsin deficiency,COPD,Gene expression,Integrative analysis,miRNAs},
  language     = {eng},
  month        = {11},
  pages        = {3381--3390},
  publisher    = {Dove Press},
  series       = {International Journal of COPD},
  title        = {Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha I-antitrypsin deficiency},
  url          = {http://dx.doi.org/10.2147/COPD.S145445},
  volume       = {12},
  year         = {2017},
}