GPIbα is the Driving Force of Hepatic Thrombopoietin Generation

Overview

Journal Res Pract Thromb Haemost

Publisher Elsevier

Date 2021 May 12

PMID 33977209

Citations 11

Authors

Danielle Karakas

Miao Xu

Heyu Ni

Affiliations

Soon will be listed here.

Abstract

Thrombopoietin (TPO), a glycoprotein hormone produced predominantly in the liver, plays important roles in the hematopoietic stem cell (HSC) niche, and is essential for megakaryopoiesis and platelet generation. Long-standing understanding proposes that TPO is constitutively produced by hepatocytes, and levels are fine-tuned through platelet and megakaryocyte internalization/degradation via the c-Mpl receptor. However, in immune thrombocytopenia (ITP) and several other diseases, TPO levels are inconsistent with this theory. Recent studies showed that platelets, besides their TPO clearance, can induce TPO production in the liver. Our group also accidentally discovered that platelet glycoprotein (GP) Ibα is required for platelet-mediated TPO generation, which is underscored in both GPIbα mice and patients with Bernard-Soulier syndrome. This review will introduce platelet versatilities and several new findings in hemostasis and platelet consumption but focus on its roles in TPO regulation. The implications of these new discoveries in hematopoiesis and the HSC niche, particularly in ITP, will be discussed.

Citing Articles

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The effects of complement-independent, autoantibody-induced apoptosis of platelets in immune thrombocytopenia (ITP).

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Plasma concentration of thrombopoietin in dogs with immune thrombocytopenia.

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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression.

Li J, Karakas D, Xue F, Chen Y, Zhu G, Yucel Y Research (Wash D C). 2023; 6:0236.

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SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19.

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