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.
journal_name
Bloodjournal_title
Bloodauthors
Evrard S,Bluteau O,Tulliez M,Rameau P,Gonin P,Zetterberg E,Palmblad J,Bonnefoy A,Villeval JL,Vainchenker W,Giraudier S,Wagner-Ballon Odoi
10.1182/blood-2010-07-294447subject
Has Abstractpub_date
2011-01-06 00:00:00pages
246-9issue
1eissn
0006-4971issn
1528-0020pii
blood-2010-07-294447journal_volume
117pub_type
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