Podocyte-Released Migrasomes in Urine Serve as an Indicator for Early Podocyte Injury.
Migrasome
Podocyte
Proteinuria
Puromycin amino nucleoside
Rac-1
Journal
Kidney diseases (Basel, Switzerland)
ISSN: 2296-9381
Titre abrégé: Kidney Dis (Basel)
Pays: Switzerland
ID NLM: 101658365
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
25
07
2020
accepted:
10
09
2020
entrez:
14
12
2020
pubmed:
15
12
2020
medline:
15
12
2020
Statut:
ppublish
Résumé
Levels of urinary microvesicles, which are increased during various kidney injuries, have diagnostic potential for renal diseases. However, the significance of urinary microvesicles as a renal disease indicator is dampened by the difficulty to ascertain their cell source. The aim of this study was to demonstrate that podocytes can release migrasomes, a unique class of microvesicle with size ranging between 400 and 2,000 nm, and the urine level of migrasomes may serve as novel non-invasive biomarker for early podocyte injury. In this study, immunofluorescence labeling, electronic microscopy, nanosite, and sequential centrifugation were used to purify and analyze migrasomes. Migrasomes released by podocytes differ from exosomes as they have different content and mechanism of release. Compared to podocytes, renal tubular cells secrete markedly less migrasomes. Moreover, secretion of migrasomes by human or murine podocytes was strongly augmented during podocyte injuries induced by LPS, puromycin amino nucleoside (PAN), or a high concentration of glucose (HG). LPS, PAN, or HG-induced podocyte migrasome release, however, was blocked by Rac-1 inhibitor. Strikingly, a higher level of podocyte migrasomes in urine was detected in mice with PAN-nephropathy than in control mice. In fact, increased urinary migrasome number was detected earlier than elevated proteinuria during PAN-nephropathy, suggesting that urinary migrasomes are a more sensitive podocyte injury indicator than proteinuria. Increased urinary migrasome number was also detected in diabetic nephropathy patients with proteinuria level <5.5 g/day. Our findings reveal that podocytes release the "injury-related" migrasomes during migration and provide urinary podocyte migrasome as a potential diagnostic marker for early podocyte injury.
Sections du résumé
BACKGROUND
BACKGROUND
Levels of urinary microvesicles, which are increased during various kidney injuries, have diagnostic potential for renal diseases. However, the significance of urinary microvesicles as a renal disease indicator is dampened by the difficulty to ascertain their cell source.
OBJECTIVES
OBJECTIVE
The aim of this study was to demonstrate that podocytes can release migrasomes, a unique class of microvesicle with size ranging between 400 and 2,000 nm, and the urine level of migrasomes may serve as novel non-invasive biomarker for early podocyte injury.
METHOD
METHODS
In this study, immunofluorescence labeling, electronic microscopy, nanosite, and sequential centrifugation were used to purify and analyze migrasomes.
RESULTS
RESULTS
Migrasomes released by podocytes differ from exosomes as they have different content and mechanism of release. Compared to podocytes, renal tubular cells secrete markedly less migrasomes. Moreover, secretion of migrasomes by human or murine podocytes was strongly augmented during podocyte injuries induced by LPS, puromycin amino nucleoside (PAN), or a high concentration of glucose (HG). LPS, PAN, or HG-induced podocyte migrasome release, however, was blocked by Rac-1 inhibitor. Strikingly, a higher level of podocyte migrasomes in urine was detected in mice with PAN-nephropathy than in control mice. In fact, increased urinary migrasome number was detected earlier than elevated proteinuria during PAN-nephropathy, suggesting that urinary migrasomes are a more sensitive podocyte injury indicator than proteinuria. Increased urinary migrasome number was also detected in diabetic nephropathy patients with proteinuria level <5.5 g/day.
CONCLUSIONS
CONCLUSIONS
Our findings reveal that podocytes release the "injury-related" migrasomes during migration and provide urinary podocyte migrasome as a potential diagnostic marker for early podocyte injury.
Identifiants
pubmed: 33313063
doi: 10.1159/000511504
pii: kdd-0006-0422
pmc: PMC7706499
doi:
Types de publication
Journal Article
Langues
eng
Pagination
422-433Informations de copyright
Copyright © 2020 by S. Karger AG, Basel.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to declare.
Références
J Diabetes Res. 2016;2016:5741518
pubmed: 28105442
J Biol Chem. 2013 Aug 9;288(32):23586-96
pubmed: 23766514
Autoimmun Rev. 2016 Jul;15(7):719-25
pubmed: 26970484
J Clin Invest. 2013 Aug;123(8):3243-53
pubmed: 23867502
Front Endocrinol (Lausanne). 2014 Oct 01;5:148
pubmed: 25324828
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228
pubmed: 29339798
J Am Heart Assoc. 2019 Jun 4;8(11):e012584
pubmed: 31433703
Nat Cell Biol. 2019 Aug;21(8):991-1002
pubmed: 31371828
Int J Biochem Cell Biol. 2014 Jan;46:9-18
pubmed: 24387844
Am J Physiol Renal Physiol. 2018 Nov 1;315(5):F1430-F1443
pubmed: 30110570
J Cell Commun Signal. 2013 Mar;7(1):49-60
pubmed: 23161414
Am J Pathol. 2018 May;188(5):1132-1148
pubmed: 29454750
Kidney Int. 2017 Aug;92(2):349-364
pubmed: 28483380
J Am Soc Nephrol. 2014 Jul;25(7):1401-7
pubmed: 24676640
Hum Pathol. 2010 Sep;41(9):1265-75
pubmed: 20447677
Am J Physiol Renal Physiol. 2017 Jan 1;312(1):F157-F171
pubmed: 27760769
J Am Soc Nephrol. 2010 Nov;21(11):1835-41
pubmed: 20576805
Kidney Int. 2016 May;89(5):1037-1048
pubmed: 27083281
JCI Insight. 2019 Mar 19;5:
pubmed: 30888336
J Am Soc Nephrol. 2016 Jan;27(1):12-26
pubmed: 26251351
World J Nephrol. 2016 Mar 6;5(2):125-38
pubmed: 26981436
Cell Discov. 2019 May 21;5:27
pubmed: 31123599
Nephron Clin Pract. 2007;106(2):c61-6
pubmed: 17570931
J Clin Invest. 1997 Jan 15;99(2):342-8
pubmed: 9006003
Kidney Int. 2001 Jun;59(6):2104-13
pubmed: 11380812
Pflugers Arch. 2017 Aug;469(7-8):951-957
pubmed: 28647853
Am J Physiol Renal Physiol. 2019 Dec 1;317(6):F1475-F1482
pubmed: 31461349
Biochem Biophys Res Commun. 2004 Jan 23;313(4):992-7
pubmed: 14706640
PLoS One. 2013 Nov 07;8(11):e80328
pubmed: 24244677
Cell Res. 2017 Nov;27(11):1397-1400
pubmed: 28829047
Am J Nephrol. 2013;37(4):302-9
pubmed: 23548793
Methods Mol Biol. 2018;1749:43-49
pubmed: 29525989
J Am Soc Nephrol. 2015 Nov;26(11):2741-52
pubmed: 25858967
Nat Commun. 2016 Mar 07;7:10872
pubmed: 26947250
PLoS One. 2014 Aug 06;9(8):e104490
pubmed: 25100147
BMC Nephrol. 2019 Aug 5;20(1):303
pubmed: 31382919
J Physiol. 2016 Oct 15;594(20):5735-5748
pubmed: 27104781
Am J Physiol Renal Physiol. 2005 Jan;288(1):F48-57
pubmed: 15339792
Eur J Immunol. 2019 Feb;49(2):323-335
pubmed: 30537116
Diabetes. 2017 May;66(5):1391-1404
pubmed: 28289043
Stem Cell Res Ther. 2017 Feb 7;8(1):24
pubmed: 28173878
J Am Soc Nephrol. 2018 Jan;29(1):155-167
pubmed: 28993503
Nat Cell Biol. 2019 Aug;21(8):966-977
pubmed: 31371827
J Diabetes Res. 2016;2016:5671803
pubmed: 26881253
Mol Cell. 2010 Jul 9;39(1):133-44
pubmed: 20603081
Nat Med. 2013 Dec;19(12):1661-6
pubmed: 24270544
Diabetologia. 2017 Mar;60(3):581-584
pubmed: 28004150
Nephrol Dial Transplant. 2017 May 1;32(5):800-807
pubmed: 27190371
Nat Commun. 2011;2:282
pubmed: 21505438
Cell Res. 2015 Jan;25(1):24-38
pubmed: 25342562