Thrombospondin-1 is not the major activator of TGF-β1 in thrombopoietin-induced myelofibrosis

Solène Evrard, Olivier Bluteau, Micheline Tulliez, Philippe Rameau, Patrick Gonin, Eva Zetterberg, Jan Palmblad, Arnaud Bonnefoy, Jean Luc Villeval, William Vainchenker, Stéphane Giraudier, Orianne Wagner-Ballon

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    19 Citations (Scopus)

    Résumé

    Transforming growth factor-β1 (TGF-β1) 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-β1 activation, we investigated the role of TSP-1 in the TPO high murine model of myelofibrosis. Two groups of engrafted mice, WT TPOhigh and Tsp-1-null TPOhigh, were constituted. All mice developed a similar myeloproliferative syndrome and an increase in total TGF-β1 levels in the plasma and in extracellular fluids of marrow and spleen. Surprisingly, we were able to detect the active form of TGF-β1 in Tsp-1-null TPOhigh mice. Accordingly, these mice developed marrow and spleen fibrosis, with intriguingly a higher grade than in WT TPOhigh mice. Our results show that TSP-1 is not the major activator of TGF-β1 in TPO-induced myelofibrosis, suggesting the contribution of another mechanism in the megakaryocyte/platelet compartment.

    langue originaleAnglais
    Pages (de - à)246-249
    Nombre de pages4
    journalBlood
    Volume117
    Numéro de publication1
    Les DOIs
    étatPublié - 6 janv. 2011

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