Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts.
Exp Hematol
; 88: 15-27, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32721504
ABSTRACT
Thrombopoietin (TPO), through activation of its cognate receptor Mpl, is the major regulator of platelet production. However, residual platelets observed in TPO- and Mpl-loss-of-function (LOF) mice suggest the existence of an additional factor to TPO in platelet production. As erythropoietin (EPO) exhibited both in vitro megakaryocytic potential, in association with other early-acting cytokines, and in vivo platelet activation activity, we sought to investigate its role in this setting. Here, we used multiple LOF models to decipher the reciprocal role of EPO and TPO in the regulation of platelet production in TPO-LOF and Mpl-LOF mice and of platelet size heterogeneity in wild-type mice. We first identified EPO as the major thrombopoietic factor in the absence of the TPO-Mpl pathway. Based on the study of several mouse models we found that the EPO-EPO receptor pathway acts on late-stage megakaryopoiesis and is responsible for large-sized platelet production, while the TPO-Mpl pathway promotes small-sized platelet production. On the basis of our data, EPO might be used for thrombocytopenia supportive therapy in congenital amegakaryocytopoiesis. Furthermore, as a distribution skewed toward large platelets is an independent risk factor and a poor prognosis indicator in atherothrombosis, the characterization of EPO's role in the production of large-sized platelets, if confirmed in humans, may open new perspectives in the understanding of the role of EPO-induced platelets in atherothrombosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trombopoetina
/
Plaquetas
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Megacariócitos
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Eritropoetina
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Trombopoese
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Hematol
Ano de publicação:
2020
Tipo de documento:
Article