Kato T, Matsumoto A, Ogami K, Tahara T, Morita H, Miyazaki H
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki, Gunma, Japan.
Stem Cells. 1998;16(5):322-8. doi: 10.1002/stem.160322.
Thrombopoietin (TPO), the c-Mpl ligand, is produced constitutively in liver and other organs, circulates in the bloodstream, and is delivered to bone marrow, where it stimulates the early development of multiple hematopoietic lineages and megakaryocytopoiesis. The concentration of TPO in blood is regulated by c-Mpl mass on platelets and megakaryocytes. In addition to regulation by the number of TPO molecules, including the possible modulation of TPO mRNA abundance in bone marrow, megakaryocytopoiesis and platelet production may be regulated as a result of modulation of TPO activity by proteolytic processing that generates truncated forms of the molecule. Characterization of TPO partially purified from human plasma, however, revealed that the full-length molecule was the predominant form in the blood of both normal individuals and thrombocytopenic patients, although small amounts of truncated species were detected. Thus, truncation of TPO, at least that in the circulation examined, does not appear to contribute to the direct regulation of platelet production in response to increased demand. Given that native TPO isolated from the plasma of thrombocytopenic animals comprises truncated forms, the truncation of TPO is likely of physiological importance in the life history of this molecule.
血小板生成素（TPO），即c-Mpl配体，在肝脏和其他器官中持续产生，在血液循环中流动，并被输送到骨髓，在那里它刺激多种造血谱系的早期发育和巨核细胞生成。血液中TPO的浓度由血小板和巨核细胞上的c-Mpl量调节。除了受TPO分子数量的调节，包括可能对骨髓中TPO mRNA丰度的调节外，巨核细胞生成和血小板生成还可能由于蛋白水解加工对TPO活性的调节而受到调节，这种加工会产生该分子的截短形式。然而，对从人血浆中部分纯化的TPO的表征显示，尽管检测到少量截短形式，但全长分子在正常人和血小板减少症患者的血液中都是主要形式。因此，TPO的截短，至少在所检测的循环中，似乎并不直接参与因需求增加而对血小板生成的调节。鉴于从血小板减少症动物血浆中分离出的天然TPO包含截短形式，TPO的截短在该分子的生命历程中可能具有重要的生理意义。
