Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD

Faiz, Alen; Steiling, Katrina; Roffel, Mirjam P.; Postma, Dirkje S.; Spira, Avrum; Lenburg, Marc E.; Borggrewe, Malte; Eijgenraam, Tim R.; Jonker, Marnix; Koppelman, Gerard H.; Pouwels, Simon D.; Liu, Gang; Alekseyev, Yuriy O.; Lam, Stephen; Hiemstra, Pieter S.; Sterk, Peter J.; Timens, Wim; Brandsma, Corry‐Anke; Heijink, Irene H.; Berge, Maarten van den

doi:10.1183/13993003.01202-2018

Cited by 30 publications

(43 citation statements)

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“…Transfection of miR-149-3p mimic into CSE-induced THP-1 cells, nonetheless, decreased the level of the proteins mentioned [48]. Bronchial biopsies from COPD patients who were treated with corticosteroids for 6 and 30 months showed increased levels of miR-320d and miR-339-3p, and decreased levels of miR-708 and miR-155 [49]. CSE stimulation of primary bronchial epithelial and BEAS-2B cells overexpressing miR-320d decreased the release of CXCL8 [49].…”

Section: Copdmentioning

confidence: 93%

“…Bronchial biopsies from COPD patients who were treated with corticosteroids for 6 and 30 months showed increased levels of miR-320d and miR-339-3p, and decreased levels of miR-708 and miR-155 [49]. CSE stimulation of primary bronchial epithelial and BEAS-2B cells overexpressing miR-320d decreased the release of CXCL8 [49]. Additionally, treatment of IL-1β to BEAS-2B cells overexpressing miR-320d downregulated the activation of NF-κB [49].…”

Section: Copdmentioning

confidence: 98%

“…CSE stimulation of primary bronchial epithelial and BEAS-2B cells overexpressing miR-320d decreased the release of CXCL8 [49]. Additionally, treatment of IL-1β to BEAS-2B cells overexpressing miR-320d downregulated the activation of NF-κB [49]. In CSE-induced human bronchial epithelial (HBE) cells, miR-218 decreased the level of mRNA and release of IL-6 and IL-8 [50].…”

Section: Copdmentioning

confidence: 99%

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miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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The development of the lung involves a diverse group of molecules that regulate cellular processes, organ formation, and maturation. The various stages of lung development are marked by accumulation of small RNAs that promote or repress underlying mechanisms, depending on the physiological environment in utero and postnatally. To some extent, the pathogenesis of various lung diseases is regulated by small RNAs. In this review, we discussed miRNAs regulation of lung development and diseases, that is, COPD, asthma, pulmonary fibrosis, and pulmonary arterial hypertension, and also highlighted possible connotations for human lung health.After fertilization in the mouse, total miRNA in the two-cell-stage embryo was demonstrated to be significantly lower than the levels in one-cell zygote [15]. Notably, total miRNA in the four-cell-stage embryo was higher than the levels in the two-cell-stage embryo [15]. In the early mouse embryo, miR-127 was upregulated at E6.5 and E7.5 [16]. Overexpression of miR-127 in mouse embryonic stem cells, which differentiated into embryoid bodies, increased the mRNA levels of Gsc, Foxa2, and Brachyury (mesendoderm markers), but elicited no change in Pax6 and Otx2 (ectoderm markers) three days after transfection. Inhibition of miR-127 showed opposite regulation of Gsc, Foxa2, and Brachyury. miR-127, moreover, was suggested to control mesendoderm differentiation [16]. miR-326 regulated sonic hedgehog signaling by targeting Smo and Gli2 [17]. The inhibition of smoothened in cultured explanted E12 mouse lung resulted in the expansion of distal epithelium, and disruption of normal branching pattern and mesenchymal integrity [17]. Another study described the functional role of miR-142-3p in the mouse embryonic lung mesenchyme. The miRNA was shown to regulate adenomatous polyposis coli to further modulate Wnt signaling [18]. Taken together, miR-142-3p regulated the proliferation and differentiation of mesenchymal progenitors in the mouse embryonic lung [18].In the developing mouse lung, the level of miR-17 was stable (E11.5-E16.5), predominantly at the pseudoglandular stage, with higher epithelial levels at E12.5 [19]. Simultaneous knockdown of miR-17 and its paralogs, miR-20a and miR-106b, for 72 h in epithelial lung explants altered branching, even in FGF10-treated condition [19]. In the human fetal lung, miR-449a was upregulated at 18-20 weeks (canalicular stage), and in the mouse embryonic lung, miR-449a level was increased from E15.5 to E18.5 [20]. The inhibition of miR-449a in E16.5 mouse lung culture (end of pseudoglandular stage) increased the mRNA levels of Mycn and Sox9, and the protein levels of Ki-67 and SOX9 particularly in the distal epithelial region [20].Knockout of miR-26a-1/miR-26a-2 in the mouse promoted the formation of dilated lumens and aerated regions at the beginning of the canalicular stage (E16.5) of lung development [21]. Results at the saccular stage (E18.5) also indicated large lamellar bodies, and increased SP-A, SP-B, and SP-C protein levels in miR-26a knockout mice....

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Section: Copdmentioning

confidence: 93%

Section: Copdmentioning

confidence: 98%

Section: Copdmentioning

confidence: 99%

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miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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“…Bronchial biopsies were taken at baseline and after 6-and 30months, amongst others for microarray gene-expression profiling. The methods for mRNA isolation, labeling, microarray hybridization (Affymetrix HuGene ST1.0 arrays) and data processing have been described previously (9,17).…”

Section: Patients and Study Design Glucold Studymentioning

confidence: 99%

Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD

Faiz

Pavlidis

Kuo

et al. 2020

Preprint

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RationaleSevere asthma and COPD share common pathophysiologic traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the U-BIOPRED cohort with one Type 2-high signature (TAC1) and 2 Type 2-low signatures. ObjectiveWe examined whether gene-expression signatures obtained in asthma can be used to identify the subgroup of COPD patients with steroid sensitivity. MethodsUsing gene set variation analysis (GSVA), we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the GLUCOLD COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment. Measurements and main resultsBronchial biopsies in COPD patients at baseline showed a wide range of expression of the 3 TACs. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 (sub)signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cellspecific genes identified by single-cell RNA-seq and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription predicted change in FEV1 %predicted following 30-month ICS±LABA. ConclusionsSputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of COPD patients and identified airway wall mast cells as a predictor of those COPD patients who will benefit from inhaled corticosteroids.Abbreviations: FEV 1 = Forced Expiratory Volume in 1second and RV/TLC= residual volume/total lung capacity .

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“…In the current issue of the European Respiratory Journal, FAIZ et al [11] report the results of a genome-wide microRNA analysis assessing the changes in microRNA profiles of bronchial biopsies from persons with moderate-to-severe COPD following 6-and 30-month treatment with an ICS. The investigators performed staged investigations of the association of 230 measured miRNAs with ICS treatment, showing four miRNAs altered in the bronchial biopsies of persons with COPD following 6-and 30-month treatment with ICS.…”

mentioning

confidence: 99%