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KMID : 1011220150020010001
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Clinical & Experimental Thrombosis and Hemostasis
2015 Volume.2 No. 1 p.1 ~ p.3
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The Ashwell-Morell Receptor and Regulation of Thrombopoietin Expression
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Song Jae-Woo
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Abstract
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Thrombopoietin (TPO) is the principal regulator of thrombopoiesis and megakaryopoiesis. TPO is mainly synthesized by hepatocyte at a relatively stable rate and little is known about the regulation of thrombopoietin levels in circulation other than the sequestration mechanism. TPO is sequestrated by TPO receptors on circulating platelets such that the TPO level rises in thrombocytopenic conditions and falls when those conditions are not present to affect thrombopoiesis and maintain platelet count. It is well known that many glycoproteins on the platelet surface are sialylated at the tips of their carbohydrate moieties and sialylation status is significantly affected by platelet storage, especially at refrigeration temperatures. Enhanced clearance of desialylated platelets from circulation has also been demonstrated. The hepatic Ashwell-Morell receptor (AMR) binds to and removes desialylated platelets. Recently it was shown that platelets gradually lose sialylation during circulation. The most fascinating and newly demonstrated phenomenon is that desialylated platelets bound to AMR induce thrombopoietin expression by the hepatocytes. For this, AMR uptake into hepatocytes is essential and regulated by JAK2 and STAT3 both in vivo and in vitro. The involvement of JAK2 in AMR-mediated thrombopoietin expression can explain how thrombocytopenia complicates JAK1/2 inhibition.
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KEYWORD
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Platelet, Ashwell-Morell receptor, Sialic acid, Thrombopoietin, Hepatocyte
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