The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling.
The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling.
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肝脏Ashwell-Morell受体（AMR）可以结合和清除脱唾液酸化的血小板。我们证明血小板在血液中循环和老化时会去唾液酸化。脱唾液酸血小板与AMR的结合诱导肝血小板生成素（TPO）基因转录和翻译，从而调节血小板生成。在体内和体外，高度保守的内吞AMR通过Janus激酶2（JAK 2）和急性期反应信号转导子和转录激活子3（STAT 3）进行信号传导。认识到这种新的生理反馈机制阐明了血小板疾病的病理生理学，如原发性血小板增多症和免疫性血小板减少症，并有助于我们了解JAK 1/2抑制剂观察到的血小板减少症的机制。
The hepatic Ashwell-Morell receptor (AMR) can bind and remove desialylated platelets. We demonstrate that platelets become desialylated as they circulate and age in blood. Binding of desialylated platelets to the AMR induces hepatic thrombopoietin (TPO) gene transcription and translation, thereby regulating platelet production. The highly conserved endocytic AMR signals 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 novel physiological feedback mechanism illuminates the pathophysiology of platelet diseases, such as Essential Thrombocythemia and Immune Thrombocytopenia, and contributes to our understanding of the mechanisms of thrombocytopenia observed with JAK1/2 inhibition.