A combination of LCPUFAs regulates the expression of miRNA-146a-5p in a murine asthma model and human alveolar cells.
Alveolar Epithelial Cells
/ drug effects
Animals
Asthma
/ drug therapy
Cell Line, Tumor
Disease Models, Animal
Epigenesis, Genetic
Fatty Acids, Unsaturated
/ pharmacology
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Lung
/ drug effects
Mice
Mice, Inbred C57BL
MicroRNAs
/ genetics
5-LO
Asthma
COX-2
LCPUFA
miR-146a
Journal
Prostaglandins & other lipid mediators
ISSN: 1098-8823
Titre abrégé: Prostaglandins Other Lipid Mediat
Pays: United States
ID NLM: 9808648
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
31
01
2019
revised:
14
08
2019
accepted:
09
09
2019
pubmed:
8
11
2019
medline:
10
4
2021
entrez:
8
11
2019
Statut:
ppublish
Résumé
LCPUFAs are suggestive of having beneficial effects on inflammatory diseases such as asthma. However, little is known about the modulative capacity of omega-(n)-3 and n-6 LCPUFAs within the epigenetic regulation of inflammatory processes. The aim of this study was to investigate whether a specific combined LCPUFA supplementation restores disease-dysregulated miRNA-profiles in asthmatic mice. In addition, we determined the effect of the LCPUFA supplementation on the interaction of the most regulated miRNA expression and oxygenase activity in vitro. Sequencing of miRNA was performed by NGS from lung tissue of asthmatic and control mice with normal diet, as well as of LCPUFA supplemented asthmatic mice. Network analysis and evaluation of the biological targets of the miRNAs were performed by DIANA- miRPath v.3 webserver software, TargetScanMouse 7.2, and tool String v.10, respectively. Expression of hsa-miRNA-146a-5p and activity of COX-2 and 5-LO in LCPUFA-treated A549 cells were assessed by qPCR and flow cytometry, respectively. In total, 62 miRNAs were dysregulated significantly in murine allergic asthma. The LCPUFA combination restored 21 of these dysregulated miRNAs, of which eight (mmu-miR-146a-5p, -30a-3p, -139-5p, -669p-5p, -145a-5p, -669a-5p, -342-3p and -15b-5p) were even normalized compared to the control levels. Interestingly, six of the eight rescued miRNAs are functionally implicated in TGF-β signaling, ECM-receptor interaction and fatty acid biosynthesis. Furthermore, in vitro experiments demonstrated that upregulation of hsa-miRNA-146a-5p is accompanied by a reduction of COX-2 and 5-LO activity. Moreover, transfection experiments revealed that LCPUFAs inhibit 5-LO activity in the presence and absence of anti-miR-146a-5p. Our results demonstrate the modulative capacity of LCPUFAs on dysregulated miRNA expression in asthma. In addition, we pointed out the high regulative potential of LCPUFAs on 5-LO regulation and provided evidence that miR-146a partly controls the regulation of 5-LO.
Sections du résumé
BACKGROUND
LCPUFAs are suggestive of having beneficial effects on inflammatory diseases such as asthma. However, little is known about the modulative capacity of omega-(n)-3 and n-6 LCPUFAs within the epigenetic regulation of inflammatory processes.
OBJECTIVE
The aim of this study was to investigate whether a specific combined LCPUFA supplementation restores disease-dysregulated miRNA-profiles in asthmatic mice. In addition, we determined the effect of the LCPUFA supplementation on the interaction of the most regulated miRNA expression and oxygenase activity in vitro.
METHODS
Sequencing of miRNA was performed by NGS from lung tissue of asthmatic and control mice with normal diet, as well as of LCPUFA supplemented asthmatic mice. Network analysis and evaluation of the biological targets of the miRNAs were performed by DIANA- miRPath v.3 webserver software, TargetScanMouse 7.2, and tool String v.10, respectively. Expression of hsa-miRNA-146a-5p and activity of COX-2 and 5-LO in LCPUFA-treated A549 cells were assessed by qPCR and flow cytometry, respectively.
RESULTS
In total, 62 miRNAs were dysregulated significantly in murine allergic asthma. The LCPUFA combination restored 21 of these dysregulated miRNAs, of which eight (mmu-miR-146a-5p, -30a-3p, -139-5p, -669p-5p, -145a-5p, -669a-5p, -342-3p and -15b-5p) were even normalized compared to the control levels. Interestingly, six of the eight rescued miRNAs are functionally implicated in TGF-β signaling, ECM-receptor interaction and fatty acid biosynthesis. Furthermore, in vitro experiments demonstrated that upregulation of hsa-miRNA-146a-5p is accompanied by a reduction of COX-2 and 5-LO activity. Moreover, transfection experiments revealed that LCPUFAs inhibit 5-LO activity in the presence and absence of anti-miR-146a-5p.
CONCLUSION
Our results demonstrate the modulative capacity of LCPUFAs on dysregulated miRNA expression in asthma. In addition, we pointed out the high regulative potential of LCPUFAs on 5-LO regulation and provided evidence that miR-146a partly controls the regulation of 5-LO.
Identifiants
pubmed: 31698144
pii: S1098-8823(19)30129-7
doi: 10.1016/j.prostaglandins.2019.106378
pii:
doi:
Substances chimiques
Fatty Acids, Unsaturated
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106378Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors do not have any competing interests to declare. The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.