Naslov
The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling

Autori
Grozovsky, Renata ; Jurak Begonja, Antonija ; Liu, Kaifeng ; Visner, Gary ; Hartwig, John . ; Falet, Hervé ; Hoffmeister, Karin M.

Izvornik
Nature medicine (1078-8956) 21 (2014), 1; 47-54

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Ashwell-Morell receptor, platelets, glycobiology

Sažetak
The hepatic Ashwell-Morell receptor (AMR) can bind and remove desialylated platelets. Here we demonstrate that platelets become desialylated as they circulate and age in blood. Binding of desialylated platelets to the AMR induces hepatic expression of thrombopoietin (TPO) mRNA and protein, thereby regulating platelet production. Endocytic AMR controls TPO expression through Janus kinase 2 (JAK2) and the acute phase response signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro. Recognition of this newly identified physiological feedback mechanism illuminates the pathophysiology of platelet diseases, such as essential thrombocythemia and immune thrombocytopenia, and contributes to an understanding of the mechanisms of thrombocytopenia observed with JAK1/2 inhibition.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA