[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.
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
F.R.S.-FNRS - Fonds de la Recherche Scientifique Fonds d’Investissement de Recherche Scientifique du Centre Hospitalier Universitaire de Liège CHU Liège - Centre Hospitalier Universitaire de Liège ULiège - Université de Liège Fonds Léon Fredericq
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Bibliography
Raghu G, Collard HR, Egan JJ, et al. An offcial ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fbrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788-824.
Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fbrosis (CAPACITY): two randomised trials. The Lancet 2011;377:1760-9.
Guiot J, Henket M, Corhay JL, et al. Sputum biomarkers in IPF: evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7. PLoS One 2017;12:e0171344.
King TE, Pardo A, Selman M. Idiopathic pulmonary fbrosis. The Lancet 2011;378:1949-61.
Wynn TA. Integrating mechanisms of pulmonary fbrosis. J Exp Med 2011;208:1339-50.
Lederer DJ, Martinez FJ, Fibrosis I P. Idiopathic pulmonary fbrosis. N Engl J Med 2018;378:1811-23.
Wilson MS, Wynn TA. Pulmonary fbrosis: pathogenesis, etiology and regulation. Mucosal Immunol 2009;2:103-21.
Kropski JA, Lawson WE, Young LR, et al. Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fbrosis. Dis Model Mech 2013;6:9-17.
Guiot J, Struman I, Chavez V, et al. Altered epigenetic features in circulating nucleosomes in idiopathic pulmonary fbrosis. Clin Epigenetics 2017;9:84.
Álvarez D, Cárdenes N, Sellarés J, et al. IPF lung fbroblasts have a senescent phenotype. Am J Physiol Lung Cell Mol Physiol 2017;313:L1164-73.
Richeldi L, Costabel U, Selman M, et al. Effcacy of a tyrosine kinase inhibitor in idiopathic pulmonary fbrosis. N Engl J Med 2011;365:1079-87.
Baek D, Villén J, Shin C, et al. The impact of microRNAs on protein output. Nature 2008;455:64-71.
Cheng HS, Njock Makon-Sbastien, Khyzha N, et al. Noncoding RNAs regulate NF-ΰB signaling to modulate blood vessel infammation. Front Genet 2014;5:422.
Makiguchi T, Yamada M, Yoshioka Y, et al. Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fbrosis. Respir Res 2016;17:110.
Yang G, Yang L, Wang W, et al. Discovery and validation of extracellular/circulating microRNAs during idiopathic pulmonary fbrosis disease progression. Gene 2015;562:138-44.
Li P, Li J, Chen T, et al. Expression analysis of serum microRNAs in idiopathic pulmonary fbrosis. Int J Mol Med 2014;33:1554-62.
Guiot J, Struman I, Louis E, et al. Exosomal miRNAs in lung diseases: from biologic function to therapeutic targets. J Clin Med 2019;8:1345.
Poulet C, Njock M-S, Moermans C, et al. Exosomal long non-coding RNAs in lung diseases. Int J Mol Sci 2020;21:3580.
Liu G, Friggeri A, Yang Y, et al. miR-21 mediates fbrogenic activation of pulmonary fbroblasts and lung fbrosis. J Exp Med 2010;207:1589-97.
Yang S, Banerjee S, de Freitas A, et al. Participation of miR-200 in pulmonary fbrosis. Am J Pathol 2012;180:484-93.
Liang H, Xu C, Pan Z, et al. The antifbrotic effects and mechanisms of microRNA-26a action in idiopathic pulmonary fbrosis. Mol Ther 2014;22:1122-33.
Xiao J, Meng X-M, Huang XR, et al. miR-29 inhibits bleomycin-induced pulmonary fbrosis in mice. Mol Ther 2012;20:1251-60.
Pandit K V, Corcoran D, Yousef H, et al. Inhibition and role of let-7d in idiopathic pulmonary fbrosis. Am J Respir Crit Care Med 2010;182:220-9.
Caby M-P, Lankar D, Vincendeau-Scherrer C, et al. Exosomal-like vesicles are present in human blood plasma. Int Immunol 2005;17:879-87.
Admyre C, Grunewald J, Thyberg J, et al. Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fuid. Eur Respir J 2003;22:578-83.
Mathivanan S, Fahner CJ, Reid GE, et al. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res 2012;40:D1241-4.
Njock M-S, Fish JE. Endothelial miRNAs as cellular messengers in cardiometabolic diseases. Trends Endocrinol Metab 2017;28:237-46.
Bovy N, Blomme B, Frères P, et al. Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer. Oncotarget 2015;6:10253-66.
Njock M-S, Cheng HS, Dang LT, et al. Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing antiinfammatory microRNAs. Blood 2015;125:3202-12.
Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell 2016;164:1226-32.
Martin-Medina A, Lehmann M, Burgy O, et al. Increased extracellular vesicles mediate Wnt5a signaling in idiopathic pulmonary fbrosis. Am J Respir Crit Care Med 2018;198:1527-38.
Tan JL, Lau SN, Leaw B, et al. Amnion epithelial cell-derived exosomes restrict lung injury and enhance endogenous lung repair. Stem Cells Transl Med 2018;7:180-96.
Njock M-S, Guiot J, Henket MA, et al. Sputum exosomes: promising biomarkers for idiopathic pulmonary fbrosis. Thorax 2019;74:309-12.
Guiot J, Duysinx B, Seidel L, et al. Clinical experience in idiopathic pulmonary fbrosis: a retrospective study. Acta Clin Belg 2018;73:139-43.
Guiot J, Demarche S, Henket M, et al. Methodology for sputum induction and laboratory processing. J Vis Exp 2017:e56612.
Maes T, Cobos FA, Schleich F, et al. Asthma infammatory phenotypes show differential microRNA expression in sputum. J Allergy Clin Immunol 2016;137:1433-46.
Squadrito ML, Baer C, Burdet F, et al. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep 2014;8:1432-46.
Khalil N, O'Connor RN, Unruh HW, et al. Increased Production and Immunohistochemical Localization of Transforming Growth Factor-α in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol 1991;5:155-62.
Broekelmann TJ, Limper AH, Colby T V, et al. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fbrosis. Proc Natl Acad Sci USA 1991;88:6642-6.
Coker RKet al. Localisation of transforming growth factor beta1 and beta3 mRNA transcripts in normal and fbrotic human lung. Thorax 2001;56:549-56.
Wang Y, Ouyang M, Wang Q, et al. MicroRNA-142-3p inhibits hypoxia/reoxygenation-induced apoptosis and fbrosis of cardiomyocytes by targeting high mobility group box 1. Int J Mol Med 2016;38:1377-86.
Yang X, Dan X, Men R, et al. Mir-142-3P blocks TGF-β-induced activation of hepatic stellate cells through targeting TGFβRI. Life Sci 2017;187:22-30.
Selman M, Pardo A. The leading role of epithelial cells in the pathogenesis of idiopathic pulmonary fbrosis. Cell Signal 2020;66:109482.
Xu Y, Mizuno T, Sridharan A, et al. Single-Cell RNA sequencing identifes diverse roles of epithelial cells in idiopathic pulmonary fbrosis. JCI Insight 2016;1:e90558.
Lu X, Wei Y, Liu F. Direct regulation of p53 by miR-142a-3p mediates the survival of hematopoietic stem and progenitor cells in zebrafsh. Cell Discov 2015;1:15027.
Guo F, Lin SC, Zhao MS, et al. microRNA-142-3p inhibits apoptosis and infammation induced by bleomycin through down-regulation of COX-2 in MLE-12 cells. Braz J Med Biol Res 2017;50:e5974.
Caporarello N, Meridew JA, Jones DL, et al. PGC1α repression in IPF fbroblasts drives a pathologic metabolic, secretory and fbrogenic state. Thorax 2019;74:749-60.
Piantadosi CA, Suliman HB. Mitochondrial dysfunction in lung pathogenesis. Annu Rev Physiol 2017;79:495-515.
Carraro G, Shrestha A, Rostkovius J, et al. miR-142-3P balances proliferation and differentiation of mesenchymal cells during lung development. Development 2014;141:1272-81.
Jin Chang'e, Xiao L, Zhou Z, et al. Mir-142-3P suppresses the proliferation, migration and invasion through inhibition of NR2F6 in lung adenocarcinoma. Hum Cell 2019;32:437-46.
Zhu K, Zhang Z, Zhang H, et al. Mir-142-3P targeting NUCKS1 inhibits proliferation and invasion of pancreatic cancer cells. Artif Cells Nanomed Biotechnol 2020;48:415-24.
Fang S, Xu C, Zhang Y, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofbroblast differentiation by inhibiting the transforming growth Factor-β/SMAD2 pathway during wound healing. Stem Cells Transl Med 2016;5:1425-39.
Shentu T-P, Huang T-S, Cernelc-Kohan M, et al. Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofbroblastic differentiation. Sci Rep 2017;7:18052.
Kulshreshtha A, Ahmad T, Agrawal A, et al. Proinfammatory role of epithelial cell-derived exosomes in allergic airway infammation. J Allergy Clin Immunol 2013;131:e14:1194-203.
Qazi KR, Torregrosa Paredes P, Dahlberg B, et al. Proinfammatory exosomes in bronchoalveolar lavage fuid of patients with sarcoidosis. Thorax 2010;65:1016-24.
Cheng HS, Sivachandran N, Lau A, et al. Micro RNA-146 represses endothelial activation by inhibiting pro-infammatory pathways. EMBO Mol Med 2013;5:1017-34.
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