Transforming growth factor-beta 1 (TGF-beta 1) induces thrombopoietin frombone marrow stromal cells, which stimulates the expression of TGF-beta receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-beta itself with high specificity

The present study was designed to test the concept that platelets release a humoral factor that plays a regulatory role in megakaryopoiesis. The resul ts showed that, among various hematoregulatory cytokines examined, transfor ming growth factor-beta 1 (TGF-beta 1) was by far the most potent enhancer of mRNA expression of bone marrow stromal thrombopoietin (TPO), a commitmen t of lineage specificity. The TPO, in turn, induced TGF-beta receptors I an d II on megakaryoblasts at the midmegakaryopoietic stage; at this stage, TG F-beta 1 was able to arrest the maturation of megakaryocyte colony-forming units (CFU-Meg), This effect was relatively specific when compared with its effect on burst-forming unit-erythroid (BFU-E) or colony-forming unit-gran ulocyte-macrophage (CFU-GM). In patients with idiopathic thrombocytopenic p urpura (ITP), the levels of both TGF-beta 1 and stromal TPO mRNA were corre latively increased and an arrest of megakaryocyte maturation was observed. These in vivo findings are in accord with the aforementioned in vitro resul ts. Thus, the results of the present investigation suggest that TGF-beta 1 is one of the pathophysiological feedback regulators of megakaryopoiesis, ( C) 1999 by The American Society of Hematology.