Platelet-instructed SPP1
CP: Immunology
CXCL4
PF4
SPP1
SPP1 macrophages
chronic kidney disease
fibrosis
heart failure
innate immunity
myocardial infarction
platelets
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 02 2023
28 02 2023
Historique:
received:
06
05
2022
revised:
11
11
2022
accepted:
31
01
2023
medline:
4
10
2023
pubmed:
23
2
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Fibrosis represents the common end stage of chronic organ injury independent of the initial insult, destroying tissue architecture and driving organ failure. Here we discover a population of profibrotic macrophages marked by expression of Spp1, Fn1, and Arg1 (termed Spp1 macrophages), which expands after organ injury. Using an unbiased approach, we identify the chemokine (C-X-C motif) ligand 4 (CXCL4) to be among the top upregulated genes during profibrotic Spp1 macrophage differentiation. In vitro and in vivo studies show that loss of Cxcl4 abrogates profibrotic Spp1 macrophage differentiation and ameliorates fibrosis after both heart and kidney injury. Moreover, we find that platelets, the most abundant source of CXCL4 in vivo, drive profibrotic Spp1 macrophage differentiation. Single nuclear RNA sequencing with ligand-receptor interaction analysis reveals that macrophages orchestrate fibroblast activation via Spp1, Fn1, and Sema3 crosstalk. Finally, we confirm that Spp1 macrophages expand in both human chronic kidney disease and heart failure.
Identifiants
pubmed: 36807143
pii: S2211-1247(23)00142-0
doi: 10.1016/j.celrep.2023.112131
pmc: PMC9992450
pii:
doi:
Substances chimiques
Ligands
0
Osteopontin
106441-73-0
Platelet Factor 4
37270-94-3
SPP1 protein, human
0
PF4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112131Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.