Beclin-1 dependent autophagy improves renal outcomes following Unilateral Ureteral Obstruction (UUO) injury.
Beclin-1
autophagy
fibrosis
kidney injury
renal transplant
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
21
11
2022
accepted:
31
01
2023
entrez:
6
3
2023
pubmed:
7
3
2023
medline:
8
3
2023
Statut:
epublish
Résumé
Interstitial Fibrosis and Tubular Atrophy (IFTA) is the most common cause of long-term graft failure following renal transplant. One of the hallmarks of IFTA is the development of interstitial fibrosis and loss of normal renal architecture. In this study, we evaluated the role of autophagy initiation factor Beclin-1 in protecting against post-renal injury fibrosis. Adult male wild type (WT) C57BL/6 mice were subjected to Unilateral Ureteral Obstruction (UUO), and kidney tissue samples were harvested at 72-hour, 1- and 3-week post-injury. The UUO-injured and uninjured kidney samples were examined histologically for fibrosis, autophagy flux, inflammation as well activation of the Integrated Stress Response (ISR). We compared WT mice with mice carrying a forced expression of constitutively active mutant form of Beclin-1, In all experiments, UUO injury induces a progressive development of fibrosis and inflammation. These pathological signs were diminished in The results suggest that UUO causes a insufficient, maladaptive renal autophagy, which triggered downstream activation of inflammatory STING pathway, production of cytokines, and pathological activation of ISR, eventually leading to the development of fibrosis. Enhancing autophagy
Sections du résumé
Background
Interstitial Fibrosis and Tubular Atrophy (IFTA) is the most common cause of long-term graft failure following renal transplant. One of the hallmarks of IFTA is the development of interstitial fibrosis and loss of normal renal architecture. In this study, we evaluated the role of autophagy initiation factor Beclin-1 in protecting against post-renal injury fibrosis.
Methods
Adult male wild type (WT) C57BL/6 mice were subjected to Unilateral Ureteral Obstruction (UUO), and kidney tissue samples were harvested at 72-hour, 1- and 3-week post-injury. The UUO-injured and uninjured kidney samples were examined histologically for fibrosis, autophagy flux, inflammation as well activation of the Integrated Stress Response (ISR). We compared WT mice with mice carrying a forced expression of constitutively active mutant form of Beclin-1,
Results
In all experiments, UUO injury induces a progressive development of fibrosis and inflammation. These pathological signs were diminished in
Conclusions
The results suggest that UUO causes a insufficient, maladaptive renal autophagy, which triggered downstream activation of inflammatory STING pathway, production of cytokines, and pathological activation of ISR, eventually leading to the development of fibrosis. Enhancing autophagy
Identifiants
pubmed: 36875088
doi: 10.3389/fimmu.2023.1104652
pmc: PMC9978333
doi:
Substances chimiques
Beclin-1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1104652Informations de copyright
Copyright © 2023 Lopez-Soler, Nikouee, Kim, Khan, Sivaraman, Ding and Zang.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Cell Mol Med. 2017 Dec;21(12):3679-3692
pubmed: 28766848
Circulation. 2021 Nov 2;144(18):1500-1515
pubmed: 34583519
Cell. 2008 Jan 11;132(1):27-42
pubmed: 18191218
Nephrology (Carlton). 2012 Feb;17(2):148-59
pubmed: 22085202
Science. 2015 Mar 13;347(6227):aaa2630
pubmed: 25636800
Cells. 2019 Feb 10;8(2):
pubmed: 30744190
N Engl J Med. 2003 Dec 11;349(24):2326-33
pubmed: 14668458
Am J Physiol Renal Physiol. 2015 Feb 1;308(3):F226-36
pubmed: 25428127
Autophagy. 2022 Feb;18(2):409-422
pubmed: 34101533
J Am Soc Nephrol. 2014 Dec;25(12):2835-46
pubmed: 24854279
Front Pharmacol. 2022 May 30;13:918732
pubmed: 35707397
Nat Rev Nephrol. 2014 Sep;10(9):493-503
pubmed: 24981817
FASEB Bioadv. 2021 Jan 25;3(3):123-135
pubmed: 33733054
Kidney Res Clin Pract. 2021 Jun;40(2):208-219
pubmed: 34024086
Kidney Int. 2022 Jan;101(1):63-78
pubmed: 34736972
J Cell Mol Med. 2018 Feb;22(2):1190-1201
pubmed: 29077259
J Virol. 1998 Nov;72(11):8586-96
pubmed: 9765397
Biomed Res Int. 2014;2014:869390
pubmed: 25254217
Adv Exp Med Biol. 2020;1207:469-480
pubmed: 32671769
Annu Rev Physiol. 2020 Feb 10;82:297-322
pubmed: 31640469
Autophagy. 2016 Jun 2;12(6):976-98
pubmed: 27123926
Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F769-F780
pubmed: 29631355
Front Cell Infect Microbiol. 2021 Jun 15;11:706637
pubmed: 34211859
Science. 2020 Apr 24;368(6489):
pubmed: 32327570
Cell Signal. 2020 Nov;75:109768
pubmed: 32896607
EMBO Rep. 2016 Oct;17(10):1374-1395
pubmed: 27629041
Cancer Lett. 2013 Nov 28;341(1):24-9
pubmed: 23612071
Cell Death Differ. 2022 Apr;29(4):750-757
pubmed: 34743204
Kidney Blood Press Res. 2022;47(4):256-269
pubmed: 35016182
Mol Med. 2011;17(11-12):1295-305
pubmed: 21863214
Cell Death Dis. 2015 Jul 30;6:e1822
pubmed: 26225772
Circulation. 2018 Nov 13;138(20):2247-2262
pubmed: 29853517
Open Med (Wars). 2021 Sep 29;16(1):1428-1437
pubmed: 34676302
Cell Rep. 2019 Oct 29;29(5):1261-1273.e6
pubmed: 31665638
Hum Genomics. 2016 Jan 07;10:2
pubmed: 26742487
Nat Rev Cancer. 2002 Jun;2(6):442-54
pubmed: 12189386
Autophagy. 2021 Jan;17(1):1-382
pubmed: 33634751
Transplant Rev (Orlando). 2008 Jan;22(1):1-5
pubmed: 18631853
Kidney Int. 2012 Dec;82(12):1271-83
pubmed: 22854643
Curr Protoc Mol Biol. 2013;Chapter 14:Unit14.15
pubmed: 23547012
J Am Soc Nephrol. 2015 Jan;26(1):20-9
pubmed: 25097209
Adv Exp Med Biol. 2019;1165:557-584
pubmed: 31399985
Nature. 1999 Dec 9;402(6762):672-6
pubmed: 10604474
Cell Death Dis. 2019 Jan 28;10(2):78
pubmed: 30692509
Liver Transpl. 2010 May;16(5):567-76
pubmed: 20440766
J Clin Invest. 2002 Aug;110(3):341-50
pubmed: 12163453
Cell Metab. 2019 Oct 1;30(4):784-799.e5
pubmed: 31474566
Am J Transplant. 2005 Jun;5(6):1367-74
pubmed: 15888043
Electrophoresis. 2012 Jan;33(2):366-9
pubmed: 22222980
Cell Death Dis. 2015 Mar 19;6:e1696
pubmed: 25789971
Biomed Eng Online. 2016 Apr 27;15:46
pubmed: 27121383
Cell Death Differ. 2015 Mar;22(3):367-76
pubmed: 25257169
J Clin Invest. 2020 Sep 1;130(9):5011-5026
pubmed: 32804155
Int J Mol Sci. 2020 May 15;21(10):
pubmed: 32429129
Matrix Biol. 2021 Jun;100-101:182-196
pubmed: 33454422
Semin Nephrol. 2014 Jan;34(1):34-41
pubmed: 24485028
J Am Heart Assoc. 2022 Jul 19;11(14):e025310
pubmed: 35861821
J Am Soc Nephrol. 2004 Feb;15(2):390-7
pubmed: 14747385
Am J Physiol Renal Physiol. 2017 Jul 1;313(1):F74-F84
pubmed: 28404589
Nature. 2018 Jun;558(7708):136-140
pubmed: 29849149