The molecular mechanisms that control thrombopoiesis
Kenneth Kaushansky
Kenneth Kaushansky
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3339-3347. https://doi.org/10.1172/JCI26674.
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Category: Review Series

The molecular mechanisms that control thrombopoiesis

Abstract

Our understanding of thrombopoiesis — the formation of blood platelets — has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances.

Authors

Kenneth Kaushansky

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Figure 1

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The regulation of thrombopoietin levels. A steady-state amount of hepati...
The regulation of thrombopoietin levels. A steady-state amount of hepatic thrombopoietin (TPO) is regulated by platelet c-Mpl receptor–mediated uptake and destruction of the hormone. Hepatic production of the hormone is depicted. Upon binding to platelet c-Mpl receptors, the hormone is removed from the circulation and destroyed, which reduces blood levels. In the presence of inflammation, IL-6 is released from macrophages and, through TNF-α stimulation, from fibroblasts and circulates to the liver to enhance thrombopoietin production. Thrombocytopenia also leads to enhanced marrow stromal cell production of thrombopoietin, although the molecular mediator(s) of this effect is not yet completely understood.