Thrombospondin-1 is not the major activator of TGF-β1 in thrombopoietin-induced myelofibrosis.
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| Abstract |
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 TPO(high) and Tsp-1-null TPO(high), 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 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-β1 in TPO-induced myelofibrosis, suggesting the contribution of another mechanism in the megakaryocyte/platelet compartment.
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| Authors | 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 |
| Journal | Blood (Blood) Vol. 117 Issue 1 Pg. 246-9 (Jan 06 2011) ISSN: 1528-0020 [Electronic] United States |
| PMID | 20944070 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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