Exosomal Long Non-Coding RNAs in Lung Diseases

Poulet, Christophe; Njock, Makon‐Sébastien; Moermans, Catherine; Louis, Édouard; Louis, Renaud; Malaise, Michel; Guiot, Julien

doi:10.3390/ijms21103580

Cited by 77 publications

(49 citation statements)

References 249 publications

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“…12 13 MiRs have emerged as potent modulators of various cellular processes such as proliferation, migration, differentiation, inflammation and their utility as biomarkers of pulmonary fibrosis is being explored. [14][15][16][17][18] Indeed, Lui et al found an upregulation of miR-21-5p in…”

Section: Introductionmentioning

confidence: 99%

Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p

Guiot

Cambier

Boeckx

et al. 2020

Thorax

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IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown.MethodsTwo independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts.ResultsExosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation analysis revealed a positive association between exosomal miR-142-3p and the percentage of macrophages from sputum of patients with IPF (r=0.576, p=0.012), suggesting macrophage origin of exosomal miR-142-3p upregulation. The overexpression of miR-142-3p in alveolar epithelial cells and lung fibroblasts was able to reduce the expression of transforming growth factor β receptor 1 (TGFβ-R1) and profibrotic genes. Furthermore, exosomes isolated from macrophages present antifibrotic properties due in part to the repression of TGFβ-R1 by miR-142-3p transfer in target cells.DiscussionOur results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts.

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Section: Introductionmentioning

confidence: 99%

Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p

Guiot

Cambier

Boeckx

et al. 2020

Thorax

Self Cite

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“…In this respect, evidences of involvement of exosomal lncRNA in lung pathologies including lung cancer, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD) are increasing [1,[11][12][13][14][15]. It has been demonstrated that the exosomal microRNAs (miRNA) and lncRNA profiles among patients with pulmonary pathologies are quite distinct than healthy individuals [12,14,16,17].…”

Section: Introductionmentioning

confidence: 99%

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

et al. 2020

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Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.

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“…As expected, TGF-β was found increased in IS of SSc patients without any difference between SSc-ILD and SSc-nonILD patients. In that context, we can hypothesize that the fibroblastic responsiveness under TGF-β stimulation could vary between patients suffering from SSc inducing a personal susceptibility to develop ILD partly induced by genetic, environmental and inflammatory factors [38][39][40]. Interestingly, we found a negative correlation between IS TGF-levels and Δ FEV-1%.…”

Section: Discussionmentioning

confidence: 65%

Inflammatory profile of induced sputum composition in systemic sclerosis: a comparison with healthy volunteers

Jacquerie

Henket

Andre

et al. 2020

Preprint

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BackgroundSystemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared.MethodsIn a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%).ResultsThe IS of SSc patients had a lower weight than HV (p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p<0.0001), TGF-β (p<0.05), IL-8 (p<0.05), YKL-40 (p<0.0001) and MMP-7 (p<0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p<0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%)(r=-0.53, p<0.01), FVC (%) (r=-0.51, p<0.01) and annualized □KCO (%) (r=0.57, p<0.05), between IS TGF-□ levels and annualized □FEV-1 (%) (r=-0.57, p<0.05), between IS IGFBP-2 levels and annualized □KCO (%) (r=0.56, p<0.05).ConclusionOur study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-□ and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.

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Exosomal Long Non-Coding RNAs in Lung Diseases

Cited by 77 publications

References 249 publications

Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p

Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

Inflammatory profile of induced sputum composition in systemic sclerosis: a comparison with healthy volunteers

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