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Thrombopoietin in thrombocytopenic mice: evidence against regulation at the
mRNA level and for a direct regulatory role of platelets
R Stoffel, A Wiestner and RC Skoda
Department of Pharmacology, University of Basel, Switzerland.
Thrombopoietin (TPO), originally described as an activity in the serum of
thrombocytopenic animals that leads to increased production of platelets,
has recently been isolated and cloned. Its closest relative in the cytokine
superfamily, erythropoietin (EPO), is transcriptionally regulated during
anemia, and it was expected that TPO would similarly be regulated during
thrombocytopenia. We induced thrombocytopenia in mice and confirmed that
TPO activity was upregulated, as determined by a bioassay. Liver and kidney
were found to be the major sources of TPO mRNA. Surprisingly, TPO mRNA in
these tissues was not upregulated in thrombocytopenic mice. Using a
sensitive RNase protection assay that can distinguish between TPO isoforms,
we found no change in the profile of mRNA for these isoforms. A
semiquantitative reverse transcription- polymerase chain reaction assay
also did not demonstrate upregulation of TPO mRNA in the spleen. Thus, the
increase of TPO activity during thrombocytopenia is not caused by
regulation at the level of TPO mRNA. Furthermore, isolated mouse platelets
absorbed high amounts of bioactive TPO out of TPO-conditioned medium in a
dose-dependent fashion. Our results are consistent with TPO protein being
regulated at a posttranscriptional level and/or directly through absorption
and metabolism by platelets.
Volume 87,
Issue 2,
pp. 567-573,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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