Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis inhibit bone marrow fibrosis development. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Hematology Année : 2007

Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis inhibit bone marrow fibrosis development.

Résumé

Myelofibrosis is characterized by excessive deposits of extracellular matrix proteins, which occur as a marrow microenvironment reactive response to cytokines released from the clonal malignant myeloproliferation. The observation that mice exposed to high systemic levels of thrombopoietin (TPO) invariably developing myelofibrosis has allowed demonstration of the crucial role of transforming growth factor (TGF)-beta1 released by hematopoietic cells in the onset of myelofibrosis. The purpose of this study was to investigate whether TGF-beta1 inhibition could directly inhibit fibrosis development in a curative approach of this mice model. An adenovirus encoding for TGF-beta1 soluble receptor (TGF-beta-RII-Fc) was injected either shortly after transplantation (preventive) or 30 days post-transplantation (curative). Mice were transplanted with syngenic bone marrow cells transduced with a retrovirus encoding for murine TPO. All mice developed a myeloproliferative syndrome. TGF-beta-RII-Fc was detected in the blood of all treated mice, leading to a dramatic decrease in TGF-beta1 level. Histological analysis show that the two approaches (curative or preventive) were successful enough to inhibit bone marrow and spleen fibrosis development in this model. However, lethality of TPO overexpression was not decreased after treatment, indicating that in this mice model, myeloproliferation rather than fibrosis was probably responsible for the lethality induced by the disorder.

Dates et versions

hal-00124207 , version 1 (12-01-2007)

Identifiants

Citer

Thomas Gastinne, Frédéric Vigant, Cecile Lavenu-Bombled, Orianne Wagner-Ballon, Micheline Tulliez, et al.. Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis inhibit bone marrow fibrosis development.. Experimental Hematology, 2007, 35 (1), pp.64-74. ⟨10.1016/j.exphem.2006.08.016⟩. ⟨hal-00124207⟩
149 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More