HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
26 05 2022
26 05 2022
Historique:
received:
14
04
2021
accepted:
22
12
2021
pubmed:
19
1
2022
medline:
31
5
2022
entrez:
18
1
2022
Statut:
ppublish
Résumé
Anemia of inflammation, also known as anemia of chronic disease, is refractory to erythropoietin (EPO) treatment, but the mechanisms underlying the EPO refractory state are unclear. Here, we demonstrate that high mobility group box-1 protein (HMGB1), a damage-associated molecular pattern molecule recently implicated in anemia development during sepsis, leads to reduced expansion and increased death of EPO-sensitive erythroid precursors in human models of erythropoiesis. HMGB1 significantly attenuates EPO-mediated phosphorylation of the Janus kinase 2/STAT5 and mTOR signaling pathways. Genetic ablation of receptor for advanced glycation end products, the only known HMGB1 receptor expressed by erythroid precursors, does not rescue the deleterious effects of HMGB1 on EPO signaling, either in human or murine precursors. Furthermore, surface plasmon resonance studies highlight the ability of HMGB1 to interfere with the binding between EPO and the EPOR. Administration of a monoclonal anti-HMGB1 antibody after sepsis onset in mice partially restores EPO signaling in vivo. Thus, HMGB1-mediated restriction of EPO signaling contributes to the chronic phase of anemia of inflammation.
Identifiants
pubmed: 35040907
pii: S0006-4971(22)00080-5
doi: 10.1182/blood.2021012048
pmc: PMC9136881
doi:
Substances chimiques
Epo protein, mouse
0
HMGB1 Protein
0
HMGB1 protein, mouse
0
Receptors, Erythropoietin
0
Erythropoietin
11096-26-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3181-3193Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR076242
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144436
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152099
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118182
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 by The American Society of Hematology.
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