Article (Scientific journals)
Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p
GUIOT, Julien; Cambier, Maureen; Boeckx, Amandine et al.
2020In Thorax, 75 (10), p. 870-881
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Keywords :
Macrophage-derived Exosomes; Pulmonary Fibrosis; miR-142-3p; Intercellular Communication; Alveolar Epithelial Cells; Lung Fibroblasts; TGFβ-R1
Abstract :
[en] Introduction: Idiopathic 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. Methods: Two 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. Results: Exosomal 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. Discussion: Our 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.
Research center :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Giga-Cancer - ULiège
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
GUIOT, Julien  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de pneumologie - allergologie
Cambier, Maureen  ;  Université de Liège - ULiège > Cancer-Molecular Angiogenesis Laboratory
Boeckx, Amandine ;  Université de Liège - ULiège > Cancer-Molecular Angiogenesis Laboratory
HENKET, Monique ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Clinique de l'asthme
Nivelles, Olivier ;  Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Département des maladies infectieuses et parasitaires (DMI)
GESTER, Fanny ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de pneumologie - allergologie
LOUIS, Edouard  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de gastroentérologie, hépatologie, onco. digestive
MALAISE, Michel ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie
Dequiedt, Franck  ;  Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
LOUIS, Renaud ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de pneumologie - allergologie
Struman, Ingrid   ;  Université de Liège - ULiège > Cancer-Molecular Angiogenesis Laboratory
NJOCK, Makon-Sébastien   ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie
 These authors have contributed equally to this work.
Language :
English
Title :
Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p
Publication date :
05 August 2020
Journal title :
Thorax
ISSN :
0040-6376
eISSN :
1468-3296
Publisher :
BMJ Publishing Group, United Kingdom
Volume :
75
Issue :
10
Pages :
870-881
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Fonds d’Investissement de Recherche Scientifique du Centre Hospitalier Universitaire de Liège
CHU Liège - Centre Hospitalier Universitaire de Liège [BE]
ULiège - Université de Liège [BE]
Fonds Léon Fredericq [BE]
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