SuPAR mediates viral response proteinuria by rapidly changing podocyte function.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 07 2023
21 07 2023
Historique:
received:
08
03
2023
accepted:
14
07
2023
medline:
24
7
2023
pubmed:
22
7
2023
entrez:
21
7
2023
Statut:
epublish
Résumé
Elevation in soluble urokinase receptor (suPAR) and proteinuria are common signs in patients with moderate to severe coronavirus disease 2019 (COVID-19). Here we characterize a new type of proteinuria originating as part of a viral response. Inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes increased suPAR levels and glomerulopathy in African green monkeys. Using an engineered mouse model with high suPAR expression, inhaled variants of SARS-CoV-2 spike S1 protein elicite proteinuria that could be blocked by either suPAR antibody or SARS-CoV-2 vaccination. In a cohort of 1991 COVID-19 patients, suPAR levels exhibit a stepwise association with proteinuria in non-Omicron, but not in Omicron infections, supporting our findings of biophysical and functional differences between variants of SARS-CoV-2 spike S1 protein and their binding to podocyte integrins. These insights are not limited to SARS-CoV-2 and define viral response proteinuria (VRP) as an innate immune mechanism and co-activation of podocyte integrins.
Identifiants
pubmed: 37479685
doi: 10.1038/s41467-023-40165-5
pii: 10.1038/s41467-023-40165-5
pmc: PMC10362037
doi:
Substances chimiques
COVID-19 Vaccines
0
Receptors, Urokinase Plasminogen Activator
0
Integrins
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
4414Subventions
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Investigateurs
Alexi Vasbinder
(A)
Elizabeth Anderson
(E)
Tonimarie Catalan
(T)
Ian Pizzo
(I)
Brayden Bitterman
(B)
Grace Erne
(G)
Kristen Machado-Diaz
(K)
Feriel Presswalla
(F)
Namratha Nelapudi
(N)
Kingsley-Michael Amadi
(KM)
Alina Bardwell
(A)
Pennelope Blakely
(P)
Yiyuan Huang
(Y)
Mousumi Banerjee
(M)
Rodica Pop-Busui
(R)
Informations de copyright
© 2023. The Author(s).
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