Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3094-3101
The role of platelet 
-granular proteins in the regulation of
thrombopoietin messenger RNA expression in human bone marrow stromal
cells
Ranita Sungaran,
Orin T. Chisholm,
Boban Markovic,
Levon M. Khachigian,
Yoshihiro Tanaka, and
Beng H. Chong
From the Center for Thrombosis and Vascular Research, Chemical
Safety and Applied Toxicology Laboratories, School of Safety Science,
The University of New South Wales; Kirin Brewery Co Ltd, Tokyo, Japan;
and the Department of Haematology, Prince of Wales Hospital, Sydney,
Australia.
Thrombopoietin (TPO), the specific cytokine that regulates platelet
production, is expressed in human bone marrow (BM), kidney, and liver.
There appears to be no regulation of TPO in the kidney and liver, but
TPO messenger RNA (mRNA) expression can be modulated in the stromal
cells of the BM. In this study, we used primary human BM stromal cells
as a model to study the regulation of TPO mRNA expression in response
to various platelet 
-granular proteins. We showed that
platelet-derived growth factor (PDGF) BB and fibroblast growth factor
(FGF) 2 stimulated TPO mRNA expression in both a dose-dependent and
time-dependent manner. The addition of 50 ng/mL of PDGF and 20 ng/mL of
FGF resulted in maximal induction of TPO mRNA expression in 4 hours. We
also found that platelet factor 4 (PF4), thrombospondin (TSP), and
transforming growth factor-beta (TGF-
) are negative modulators of
megakaryocytopoiesis. We observed suppression in TPO mRNA expression
with 1 µg/mL of both PF4 and TSP and 50 ng/mL of TGF-, with
maximal suppression occurring 4 hours after the addition of these
proteins. Finally, the addition of whole-platelet lysate produced a
dose-dependent inhibition of TPO expression. On the basis of these
findings, we propose that the platelet -granular proteins studied
may regulate TPO gene expression in BM stromal cells by means of a
feedback mechanism.
