Transforming Growth Factor-ß1 (TGF-ß1) Induces Thrombopoietin From Bone Marrow Stromal Cells, Which Stimulates the Expression of TGF-ß Receptor on Megakaryocytes and, in Turn, Renders Them Susceptible to Suppression by TGF-ß Itself With High Specificity

Autor: Sakamaki, Sumio, Hirayama, Yasuo, Matsunaga, Takuya, Kuroda, Hiroyuki, Kusakabe, Toshiro, Akiyama, Takehide, Konuma, Yuichi, Sasaki, Katsunori, Tsuji, Naoki, Okamoto, Tetsuro, Kobune, Masayoshi, Kogawa, Katsuhisa, Kato, Junji, Takimoto, Rishu, Koyama, Ryuzo, Niitsu, Yoshiro
Zdroj: Blood; September 1999, Vol. 94 Issue: 6 p1961-1970, 10p
Abstrakt: The present study was designed to test the concept that platelets release a humoral factor that plays a regulatory role in megakaryopoiesis. The results showed that, among various hematoregulatory cytokines examined, transforming growth factor-ß1 (TGF-ß1) was by far the most potent enhancer of mRNA expression of bone marrow stromal thrombopoietin (TPO), a commitment of lineage specificity. The TPO, in turn, induced TGF-ß receptors I and II on megakaryoblasts at the midmegakaryopoietic stage; at this stage, TGF-ß1 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–granulocyte-macrophage (CFU-GM). In patients with idiopathic thrombocytopenic purpura (ITP), the levels of both TGF-ß1 and stromal TPO mRNA were correlatively increased and an arrest of megakaryocyte maturation was observed. These in vivo findings are in accord with the aforementioned in vitro results. Thus, the results of the present investigation suggest that TGF-ß1 is one of the pathophysiological feedback regulators of megakaryopoiesis.
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