Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis

Clarifying inflammatory processes and categorising asthma into phenotypes and endotypes improves asthma management. Obesity worsens severe asthma and reduces quality of life, although its specific molecular impact remains unclear. We previously demonstrated that hsa-miR-26a-1-3p and hsa-miR-376a-3p,...

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Main Authors: Marta Gil-Martínez, Clara Lorente-Sorolla, José M. Rodrigo-Muñoz, Sara Naharro, Zahara García-de Castro, Joaquín Sastre, Marcela Valverde-Monge, Santiago Quirce, María L. Caballero, José M. Olaguibel, Victoria del Pozo
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/14/11620
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author Marta Gil-Martínez
Clara Lorente-Sorolla
José M. Rodrigo-Muñoz
Sara Naharro
Zahara García-de Castro
Joaquín Sastre
Marcela Valverde-Monge
Santiago Quirce
María L. Caballero
José M. Olaguibel
Victoria del Pozo
author_facet Marta Gil-Martínez
Clara Lorente-Sorolla
José M. Rodrigo-Muñoz
Sara Naharro
Zahara García-de Castro
Joaquín Sastre
Marcela Valverde-Monge
Santiago Quirce
María L. Caballero
José M. Olaguibel
Victoria del Pozo
author_sort Marta Gil-Martínez
collection DOAJ
description Clarifying inflammatory processes and categorising asthma into phenotypes and endotypes improves asthma management. Obesity worsens severe asthma and reduces quality of life, although its specific molecular impact remains unclear. We previously demonstrated that hsa-miR-26a-1-3p and hsa-miR-376a-3p, biomarkers related to an inflammatory profile, discriminate eosinophilic from non-eosinophilic asthmatics. We aimed to study hsa-miR-26a-1-3p, hsa-miR-376a-3p, and their target genes in asthmatic subjects with or without obesity to find biomarkers and comprehend obese asthma mechanisms. Lung tissue samples were obtained from asthmatic patients (n = 16) and healthy subjects (n = 20). We measured miRNA expression using RT-qPCR and protein levels (IGF axis) by ELISA in confirmation samples from eosinophilic (n = 38) and non-eosinophilic (n = 39) obese (n = 26) and non-obese (n = 51) asthma patients. Asthmatic lungs showed higher hsa-miR-26a-1-3p and hsa-miR-376a-3p expression than healthy lungs. A study of seven genes regulated by these miRNAs revealed differential expression of <i>IGFBP3</i> between asthma patients and healthy individuals. In obese asthma patients, we found higher hsa-miR-26a-1-3p and IGF-1R values and lower values for hsa-miR-376a-3p and IGFBP-3. Hsa-miR-26a-1-3p and IGFBP-3 were directly and inversely correlated with body mass index, respectively. Hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used as biomarkers to phenotype patients with eosinophilic and non-eosinophilic asthma in relation to comorbid obesity.
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spelling doaj.art-57f41f967ea54b56b8d1e7fe390b188c2023-11-18T19:42:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141162010.3390/ijms241411620Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF AxisMarta Gil-Martínez0Clara Lorente-Sorolla1José M. Rodrigo-Muñoz2Sara Naharro3Zahara García-de Castro4Joaquín Sastre5Marcela Valverde-Monge6Santiago Quirce7María L. Caballero8José M. Olaguibel9Victoria del Pozo10Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainImmunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainImmunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainImmunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainImmunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainCIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, SpainCIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, SpainCIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, SpainCIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, SpainCIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, SpainImmunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainClarifying inflammatory processes and categorising asthma into phenotypes and endotypes improves asthma management. Obesity worsens severe asthma and reduces quality of life, although its specific molecular impact remains unclear. We previously demonstrated that hsa-miR-26a-1-3p and hsa-miR-376a-3p, biomarkers related to an inflammatory profile, discriminate eosinophilic from non-eosinophilic asthmatics. We aimed to study hsa-miR-26a-1-3p, hsa-miR-376a-3p, and their target genes in asthmatic subjects with or without obesity to find biomarkers and comprehend obese asthma mechanisms. Lung tissue samples were obtained from asthmatic patients (n = 16) and healthy subjects (n = 20). We measured miRNA expression using RT-qPCR and protein levels (IGF axis) by ELISA in confirmation samples from eosinophilic (n = 38) and non-eosinophilic (n = 39) obese (n = 26) and non-obese (n = 51) asthma patients. Asthmatic lungs showed higher hsa-miR-26a-1-3p and hsa-miR-376a-3p expression than healthy lungs. A study of seven genes regulated by these miRNAs revealed differential expression of <i>IGFBP3</i> between asthma patients and healthy individuals. In obese asthma patients, we found higher hsa-miR-26a-1-3p and IGF-1R values and lower values for hsa-miR-376a-3p and IGFBP-3. Hsa-miR-26a-1-3p and IGFBP-3 were directly and inversely correlated with body mass index, respectively. Hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used as biomarkers to phenotype patients with eosinophilic and non-eosinophilic asthma in relation to comorbid obesity.https://www.mdpi.com/1422-0067/24/14/11620asthma phenotypes/endotypeseosinophilic asthmaobese asthmaserum microRNAsbiomarkersIGF axis
spellingShingle Marta Gil-Martínez
Clara Lorente-Sorolla
José M. Rodrigo-Muñoz
Sara Naharro
Zahara García-de Castro
Joaquín Sastre
Marcela Valverde-Monge
Santiago Quirce
María L. Caballero
José M. Olaguibel
Victoria del Pozo
Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis
International Journal of Molecular Sciences
asthma phenotypes/endotypes
eosinophilic asthma
obese asthma
serum microRNAs
biomarkers
IGF axis
title Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis
title_full Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis
title_fullStr Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis
title_full_unstemmed Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis
title_short Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis
title_sort obese asthma phenotype is associated with hsa mir 26a 1 3p and hsa mir 376a 3p modulating the igf axis
topic asthma phenotypes/endotypes
eosinophilic asthma
obese asthma
serum microRNAs
biomarkers
IGF axis
url https://www.mdpi.com/1422-0067/24/14/11620
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