Thrombospondin-1 is not the major activator of TGF-ß1 in thrombopoietin-induced myelofibrosis.
Blood
; 117(1): 246-9, 2011 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-20944070
Transforming growth factor-ß1 (TGF-ß1) is the most important cytokine involved in the promotion of myelofibrosis. Mechanisms leading to its local activation in the bone marrow environment remain unclear. As a recent study has highlighted the role of thrombospondin-1 (TSP-1) in platelet-derived TGF-ß1 activation, we investigated the role of TSP-1 in the TPO(high) murine model of myelofibrosis. Two groups of engrafted mice, WT TPO(high) and Tsp-1-null TPO(high), were constituted. All mice developed a similar myeloproliferative syndrome and an increase in total TGF-ß1 levels in the plasma and in extracellular fluids of marrow and spleen. Surprisingly, we were able to detect the active form of TGF-ß1 in Tsp-1-null TPO(high) mice. Accordingly, these mice developed marrow and spleen fibrosis, with intriguingly a higher grade than in WT TPO(high) mice. Our results show that TSP-1 is not the major activator of TGF-ß1 in TPO-induced myelofibrosis, suggesting the contribution of another mechanism in the megakaryocyte/platelet compartment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trombopoetina
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Trombospondina 1
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Fator de Crescimento Transformador beta1
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Mielofibrose Primária
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
França