Urine-derived exosomes from individuals with IPF carry pro-fibrotic cargo.
Fibrosis
Urine
cell biology
exosomes
human
medicine
microRNA
mouse
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
received:
17
04
2022
accepted:
31
10
2022
entrez:
1
12
2022
pubmed:
2
12
2022
medline:
6
12
2022
Statut:
epublish
Résumé
MicroRNAs (miRNA) and other components contained in extracellular vesicles may reflect the presence of a disease. Lung tissue, sputum, and sera of individuals with idiopathic pulmonary fibrosis (IPF) show alterations in miRNA expression. We designed this study to test whether urine and/or tissue derived exosomal miRNAs from individuals with IPF carry cargo that can promote fibrosis. Exosomes were isolated from urine (U-IPFexo), lung tissue myofibroblasts (MF-IPFexo), serum from individuals with IPF (n=16) and age/sex-matched controls without lung disease (n=10). We analyzed microRNA expression of isolated exosomes and their in vivo bio-distribution. We investigated the effect on ex vivo skin wound healing and in in vivo mouse lung models. U-IPFexo or MF-IPFexo expressed Our results provide evidence of a systemic feature of IPF whereby exosomes contain pro-fibrotic miRNAs when obtained from a fibrotic source and interfere with response to tissue injury as measured in skin and lung models. This work was supported in part by Lester and Sue Smith Foundation and The Samrick Family Foundation and NIH grants R21 AG060338 (SE and MKG), U01 DK119085 (IP, RS, MTC).
Sections du résumé
Background
MicroRNAs (miRNA) and other components contained in extracellular vesicles may reflect the presence of a disease. Lung tissue, sputum, and sera of individuals with idiopathic pulmonary fibrosis (IPF) show alterations in miRNA expression. We designed this study to test whether urine and/or tissue derived exosomal miRNAs from individuals with IPF carry cargo that can promote fibrosis.
Methods
Exosomes were isolated from urine (U-IPFexo), lung tissue myofibroblasts (MF-IPFexo), serum from individuals with IPF (n=16) and age/sex-matched controls without lung disease (n=10). We analyzed microRNA expression of isolated exosomes and their in vivo bio-distribution. We investigated the effect on ex vivo skin wound healing and in in vivo mouse lung models.
Results
U-IPFexo or MF-IPFexo expressed
Conclusions
Our results provide evidence of a systemic feature of IPF whereby exosomes contain pro-fibrotic miRNAs when obtained from a fibrotic source and interfere with response to tissue injury as measured in skin and lung models.
Funding
This work was supported in part by Lester and Sue Smith Foundation and The Samrick Family Foundation and NIH grants R21 AG060338 (SE and MKG), U01 DK119085 (IP, RS, MTC).
Identifiants
pubmed: 36454035
doi: 10.7554/eLife.79543
pii: 79543
pmc: PMC9714968
doi:
pii:
Substances chimiques
Gold
7440-57-5
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Elliot et al.
Déclaration de conflit d'intérêts
SE holds pending patent applications for Family - Mesenchymal stem cell-derived extracellular vesicles and uses thereof for treating and diagnosing fibrotic diseases (30309-001*), Family - Diagnostic and therapeutic uses of compositions comprising purified, enriched potent exosomes containing disease-based and therapy based signature cargo (130309-003*), and Family - Urine-derived exosomes from individuals with IPF carry pro-fibrotic cargo and impair tissue repair (130309-004*), PC, SP, XX, SS, ER, SH, JP, RS, IP No competing interests declared, JL ZenBio, SD participated on a paid role on the Scientific Advisory Board for Akron Biotech and roles on the Scientific Advisory Board for ICN2 and on the Board of Trustees for BIST. SD also received payments/stock options from Berg Pharma and stock options from Aanika Biosciences. The author has no other competing interests to declare, MT DSMB, provisional patent, NIH support, MG holds pending patent applications for Family - Mesenchymal stem cell-derived extracellular vesicles and uses thereof for treating and diagnosing fibrotic diseases (30309-001*), Family - Diagnostic and therapeutic uses of compositions comprising purified, enriched potent exosomes containing disease-based and therapy based signature cargo (130309-003*), and Family - Urine-derived exosomes from individuals with IPF carry pro-fibrotic cargo and impair tissue repair (130309-004*). MKG has a role as Chair, DMSB, Medical College of South Carolina, Mesenchymal Stem Cells in Type I Diabetes (T1D) Phase 1 trial (July 2019-present). The author has no other competing interests to declare
Références
Int J Mol Med. 2014 May;33(5):1055-63
pubmed: 24573178
J Cell Physiol. 2018 Aug;233(8):5503-5512
pubmed: 29271488
Nat Rev Dis Primers. 2017 Oct 20;3:17074
pubmed: 29052582
Genes (Basel). 2020 Feb 18;11(2):
pubmed: 32085655
J Clin Med. 2019 Aug 29;8(9):
pubmed: 31470655
J Cell Sci. 2015 Sep 1;128(17):3197-209
pubmed: 26163491
Mol Endocrinol. 2010 Nov;24(11):2152-65
pubmed: 20810711
J Transl Med. 2011 Jun 08;9:86
pubmed: 21651777
PLoS One. 2016 Jan 22;11(1):e0147236
pubmed: 26800519
RNA. 2018 Mar;24(3):423-435
pubmed: 29282313
Eur Respir J. 2013 Oct;42(4):916-23
pubmed: 23598958
Int J Mol Sci. 2019 Mar 22;20(6):
pubmed: 30909462
Curr Opin Pharmacol. 2019 Dec;49:110-115
pubmed: 31756570
Front Pharmacol. 2015 Nov 05;6:254
pubmed: 26594173
Nat Commun. 2020 Apr 21;11(1):1920
pubmed: 32317643
Front Physiol. 2012 Mar 19;3:49
pubmed: 22457651
J Clin Pathol. 1988 Apr;41(4):467-70
pubmed: 3366935
Cells. 2021 Jul 06;10(7):
pubmed: 34359876
JCI Insight. 2019 Nov 14;4(22):
pubmed: 31600171
PLoS One. 2010 Jul 27;5(7):e11803
pubmed: 20668554
Cells. 2020 Jun 26;9(6):
pubmed: 32604783
Biol Direct. 2013 Jun 07;8:12
pubmed: 23758897
Am J Respir Crit Care Med. 2018 Dec 15;198(12):1527-1538
pubmed: 30044642
Am J Respir Cell Mol Biol. 2016 Dec;55(6):759-766
pubmed: 27603223
Am J Physiol Lung Cell Mol Physiol. 2017 Nov 1;313(5):L796-L806
pubmed: 28775096
Eur Respir J. 2015 Oct;46(4):1150-66
pubmed: 25929950
PLoS One. 2016 Jun 30;11(6):e0158367
pubmed: 27362652
Thorax. 2019 Feb;74(2):132-140
pubmed: 30366970
Transl Res. 2021 Feb;228:1-12
pubmed: 32711186
J Cell Biochem. 2013 Jun;114(6):1336-42
pubmed: 23238947
Mol Genet Genomics. 2014 Dec;289(6):1225-35
pubmed: 25012394
ACS Nano. 2017 Nov 28;11(11):10883-10893
pubmed: 28960957
Eur Respir J. 2016 Jul;48(1):179-86
pubmed: 27126689
Cells. 2019 Apr 03;8(4):
pubmed: 30987213
Curr Top Med Chem. 2016;16(14):1587-98
pubmed: 26420365
Gene. 2015 May 10;562(1):138-44
pubmed: 25725128
Am J Physiol Lung Cell Mol Physiol. 2018 Apr 1;314(4):L642-L653
pubmed: 29351446
J Cell Biol. 2013 Feb 18;200(4):373-83
pubmed: 23420871
Sci Adv. 2020 Jul 08;6(28):eaba1972
pubmed: 32832598
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Am J Pathol. 2006 Aug;169(2):351-61
pubmed: 16877338
Allergy. 2021 Jun;76(6):1661-1678
pubmed: 33128813
Endocrinology. 2014 Feb;155(2):441-8
pubmed: 24274985
World J Methodol. 2013 Mar 26;3(1):11-8
pubmed: 25237619
Am J Pathol. 2017 May;187(5):1016-1034
pubmed: 28273432
Methods Mol Biol. 2013;1037:255-64
pubmed: 24029940
Am J Respir Crit Care Med. 2022 May 1;205(9):e18-e47
pubmed: 35486072
Cancer Res. 2016 Dec 1;76(23):6816-6827
pubmed: 27760789
Am J Respir Cell Mol Biol. 2011 Aug;45(2):287-94
pubmed: 20971881
Biotechnol J. 2018 Jan;13(1):
pubmed: 28865134
Transl Res. 2015 Dec;166(6):554-67
pubmed: 26432923
Respiration. 2018;96(4):338-347
pubmed: 30130749
Am J Respir Crit Care Med. 2010 Jul 15;182(2):220-9
pubmed: 20395557
Lancet. 2017 May 13;389(10082):1941-1952
pubmed: 28365056
J Extracell Vesicles. 2015 May 14;4:27066
pubmed: 25979354
Thorax. 2019 Mar;74(3):309-312
pubmed: 30244194
J Cell Physiol. 2016 Nov;231(11):2452-63
pubmed: 26916741
J Exp Med. 2020 Feb 13;217(3):e20190103
pubmed: 32997468
Front Med (Lausanne). 2020 Dec 23;7:603047
pubmed: 33425948
Proc Natl Acad Sci U S A. 2018 Oct 30;115(44):E10427-E10436
pubmed: 30327348
Expert Rev Respir Med. 2019 Mar;13(3):291-300
pubmed: 30686114
EMBO Mol Med. 2014 Sep 19;6(10):1347-56
pubmed: 25239947
J Clin Invest. 2012 Jun;122(6):1973-90
pubmed: 22622040
JCI Insight. 2019 Aug 8;5:
pubmed: 31393853
Int J Mol Sci. 2017 Mar 02;18(3):
pubmed: 28257101
PLoS One. 2019 Nov 25;14(11):e0225422
pubmed: 31765403
Comp Med. 2019 Apr 1;69(2):95-102
pubmed: 30808435
Int J Mol Sci. 2017 Aug 25;18(9):
pubmed: 28841158
N Engl J Med. 2018 Aug 23;379(8):797-798
pubmed: 30134133
Am J Pathol. 2002 May;160(5):1877-85
pubmed: 12000739
Int J Mol Sci. 2016 May 18;17(5):
pubmed: 27213331
Matrix Biol. 2018 Aug;68-69:404-421
pubmed: 29408012
Biochem Cell Biol. 2015 Apr;93(2):129-37
pubmed: 25557625
Am J Respir Crit Care Med. 2019 Nov 15;200(10):1246-1257
pubmed: 31291549
PLoS One. 2014 Jun 11;9(2):e98644
pubmed: 24918752
Drug Discov Today Dis Models. 2013 Fall;10(3):e145-e151
pubmed: 25328532