Notch3 expression in capillary pericytes predicts worse graft outcome in human renal grafts with antibody-mediated rejection.
Notch3
antibody-mediated graft rejection
kidney
pericytes
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
04
03
2022
received:
25
11
2021
accepted:
22
03
2022
pubmed:
26
5
2022
medline:
9
6
2022
entrez:
25
5
2022
Statut:
ppublish
Résumé
Microvasculature consisting of endothelial cells and pericytes is the main site of injury during antibody-mediated rejection (ABMR) of renal grafts. Little is known about the mechanisms of activation of pericytes in this pathology. We have found recently that activation of Notch3, a mediator of vascular smooth muscle cell proliferation and dedifferentiation, promotes renal inflammation and fibrosis and aggravates progression of renal disease. Therefore, we studied the pericyte expression of Notch3 in 49 non-selected renal graft biopsies (32 for clinical cause, 17 for graft surveillance). We analysed its relationship with patients' clinical and morphological data, and compared with the expression of partial endothelial mesenchymal transition (pEndMT) markers, known to reflect endothelial activation during ABMR. Notch3 was de novo expressed in pericytes of grafts with ABMR, and was significantly correlated with the microcirculation inflammation scores of peritubular capillaritis and glomerulitis and with the expression of pEndMT markers. Notch3 expression was also associated with graft dysfunction and proteinuria at the time of biopsy and in the long term. Multivariate analysis confirmed pericyte expression of Notch3 as an independent risk factor predicting graft loss. These data suggest that Notch3 is activated in the pericytes of renal grafts with ABMR and is associated with poor graft outcome.
Identifiants
pubmed: 35611804
doi: 10.1111/jcmm.17325
pmc: PMC9170800
doi:
Substances chimiques
Antibodies
0
Biomarkers
0
NOTCH3 protein, human
0
Receptor, Notch3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3203-3212Subventions
Organisme : Institut National de la Santé et de la Recherche Médicale
Organisme : Sorbonne Université
Organisme : Agence Nationale de la Recherche
Informations de copyright
© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
J Am Soc Nephrol. 2015 Jul;26(7):1561-75
pubmed: 25421557
J Vasc Res. 2014;51(4):247-58
pubmed: 25195856
Am J Transplant. 2018 Feb;18(2):293-307
pubmed: 29243394
J Pathol. 2012 Nov;228(3):286-99
pubmed: 22806125
Am J Transplant. 2008 Apr;8(4):753-60
pubmed: 18294345
Hum Immunol. 2012 Dec;73(12):1261-8
pubmed: 22863981
Am J Transplant. 2020 Sep;20(9):2400-2412
pubmed: 32167213
Nat Med. 2009 Nov;15(11):1289-97
pubmed: 19855400
Curr Opin Nephrol Hypertens. 2013 Jul;22(4):471-80
pubmed: 23722183
EMBO J. 2000 Jul 3;19(13):3337-48
pubmed: 10880446
Am J Transplant. 2014 Feb;14(2):272-83
pubmed: 24472190
Am J Transplant. 2009 Nov;9(11):2520-31
pubmed: 19843030
Am J Transplant. 2009 Oct;9(10):2312-23
pubmed: 19681822
World J Gastroenterol. 2012 Mar 28;18(12):1397-403
pubmed: 22493555
J Clin Invest. 2015 Oct 26;125(12):4514-28
pubmed: 26517696
Front Immunol. 2018 May 23;9:1130
pubmed: 29875776
J Am Soc Nephrol. 2012 May;23(5):868-83
pubmed: 22383695
Hypertension. 2011 Jun;57(6):1176-82
pubmed: 21518968
Am J Transplant. 2016 Nov;16(11):3079-3085
pubmed: 27037759
Hum Immunol. 2012 Dec;73(12):1218-25
pubmed: 22863448
Nat Rev Immunol. 2005 Oct;5(10):807-17
pubmed: 16175181
J Clin Invest. 2000 Mar;105(5):597-605
pubmed: 10712431
Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2216-24
pubmed: 18818417
Kidney Int. 2018 Jul;94(1):126-138
pubmed: 29751972
Am J Transplant. 2019 Sep;19(9):2434-2445
pubmed: 30836425
EMBO J. 2006 Mar 8;25(5):1000-8
pubmed: 16498412
J Cell Mol Med. 2022 Jun;26(11):3203-3212
pubmed: 35611804
J Am Soc Nephrol. 2016 Jan;27(1):324-32
pubmed: 25995444
Lancet. 1997 Nov 22;350(9090):1511-5
pubmed: 9388399
Science. 1999 Apr 30;284(5415):770-6
pubmed: 10221902
J Immunol. 2008 Feb 15;180(4):2214-24
pubmed: 18250428
Hypertension. 2016 Aug;68(2):392-400
pubmed: 27296994
Am J Pathol. 2010 Jan;176(1):85-97
pubmed: 20008127
Am J Transplant. 2018 Dec;18(12):2849-2856
pubmed: 30133953
Curr Opin Nephrol Hypertens. 2012 May;21(3):264-71
pubmed: 22388553
Hum Immunol. 2005 Apr;66(4):334-42
pubmed: 15866695