First published online February 14, 2008
Stem Cells
Vol. 26 No.
4
April 2008, pp.
912
-919
doi:10.1634/stemcells.2007-0777; www.StemCells.com
© 2008 AlphaMed Press
OPEN ACCESS ARTICLE
Thrombopoietin Inhibits Murine Mast Cell Differentiation
Fabrizio Martellia,
Barbara Ghinassia,b,
Rodolfo Lorenzinic,
Alessandro M. Vannucchid,
Rosa Alba Ranab,
Mitsuo Nishikawae,
Sandra Partamianf,
Giovanni Migliacciog,
Anna Rita Migliaccioa,f,h
Departments of aHematology, Oncology and Molecular Medicine,
gCell Biology and Neurosciences, and
cQuality and Safety of Animal Experimentation, Istituto Superiore Sanità, Rome, Italy;
dDepartment of Hematology, University of Florence, Florence, Italy;
bDepartment of Biomorphology, University of Chieti, Chieti, Italy;
eKirin Brewery Pharmaceutical Research Laboratory, Gunma, Japan;
fDepartment of Medicine, Mont Sinai School of Medicine, New York, New York, USA;
hMyeloproliferative Disease–Research Consortium
Key Words. Thrombopoietin • Mpl • Mast cells • Apoptosis • Bcl2 • Mitf
Correspondence:
Correspondence: Anna Rita Migliaccio, Ph.D., Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA. Telephone: 212-241-46974; Fax: 0039-0649903160; e-mail: annarita.migliaccio{at}mssm.edu
Received on September 18, 2007;
accepted for publication on January 31, 2008.
First published online in STEM CELLS EXPRESS February 14, 2008.
We have recently shown that Mpl, the thrombopoietin receptor, is expressed on murine mast cells and on their precursors and that targeted deletion of the Mpl gene increases mast cell differentiation in mice. Here we report that treatment of mice with thrombopoietin or addition of this growth factor to bone marrow-derived mast cell cultures severely hampers the generation of mature cells from their precursors by inducing apoptosis. Analysis of the expression profiling of mast cells obtained in the presence of thrombopoietin suggests that thrombopoietin induces apoptosis of mast cells by reducing expression of the transcription factor Mitf and its target antiapoptotic gene Bcl2.
Disclosure of potential conflicts of interest is found at the end of this article.
Copyright © 2008 by AlphaMed Press.