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Plasma miR-199a-5p is increased in neutrophilic phenotype asthma patients and negatively correlated with pulmonary function.
- Source :
-
PloS one [PLoS One] 2018 Mar 05; Vol. 13 (3), pp. e0193502. Date of Electronic Publication: 2018 Mar 05 (Print Publication: 2018). - Publication Year :
- 2018
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Abstract
- Objective: We investigated the relationship between plasma miRNAs levels and inflammatory characteristics in asthmatic patients.<br />Methods: Eligible adults with untreated asthma (n = 35) underwent a clinical assessment, sputum induction, and assessment of pulmonary function test and Asthma Control Test (ACT) scores. Asthma phenotypes were defined using the sputum cell count. miR-199a-5p expression was measured using quantitative real-time polymerase chain reaction (qPCR). Lipopolysaccharide (LPS) stimulation was used to detect miR-199a-5p secretion from peripheral blood-derived neutrophil, lymphocyte, macrophage and BEAS-2B cells. The correlation of miR-199a-5p expression with clinical parameters was analyzed using multiple linear regression analysis. In silico analysis predicted the target genes and signaling pathway of miR-199a-5p. Transfection of miR-199a-5p mimics in human airway smooth muscle cells (HASMCs) was performed in vitro.<br />Results: The miRNA-199a-5p levels in plasma and sputum increased significantly in patients with neutrophilic asthma compared to healthy subjects (ps = 0.014 and 0.006, respectively). Expression of miR-199a-5p in the plasma of asthmatic patients positively correlated with sputum miR-199a-5p expression (r = 0.511, p = 0.021). The miR-199a-5p level was only elevated with LPS stimulation in neutrophils but not macrophages, lymphocytes, or epithelial cells from healthy controls (p < 0.01). miR-199a-5p expression increased in response to LPS (p = 0.005) and LPS combined with IL-4 (p = 0.003), but not IL-4 alone. However, peripheral neutrophils from eosinophilic asthma patients did not respond to LPS with increased miR-199a-5p expression (n = 5, p > 0.05) in contrast to the significant response from neutrophilic patients (n = 4, p < 0.0001). miR-199a-5p negatively correlated with FEV1, FVC and PEF (r = -0.377, p = 0.026; r = -0.419, p = 0.012; and r = -0.392, p = 0.024, respectively). Multivariate correlation analysis confirmed that the plasma miR-199a-5p levels negatively correlated with FEV1 in patients with asthma (Adjusted R2 = 0.164, p = 0.015). In silico analysis suggested that the WNT signaling pathway participates in miR-199a-5p mediation of smooth muscle cell hypertrophy. In vitro experiment, miR-199a-5p mimics inhibited the protein expressions of WNT2 and WNT4, decreased the c-myc expression and dramatically increased the Sm-MHC expression in HASMCs.<br />Conclusion: Plasma miR-199a-5p was increased in neutrophilic asthma and negatively correlated with pulmonary function, which suggests that miR-199a-5p actively contributes to disease pathogenesis by modulating the inflammatory process and transferring the signal from inflammatory cells to structure cells.
- Subjects :
- Adult
Asthma genetics
Asthma immunology
Female
Gene Expression Regulation
Humans
Lipopolysaccharides pharmacology
Lung drug effects
Male
Middle Aged
Neutrophils drug effects
Sputum metabolism
Wnt2 Protein metabolism
Wnt4 Protein metabolism
Asthma blood
Asthma physiopathology
Lung physiopathology
MicroRNAs blood
Neutrophils metabolism
Phenotype
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 13
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 29505605
- Full Text :
- https://doi.org/10.1371/journal.pone.0193502