GPIbα is required for platelet-mediated hepatic thrombopoietin generation

著者: Miao Xu, June Li, Miguel A. D. Neves, Guangheng Zhu, Naadiya Carrim, Ruoying Yu, Sahil Gupta, John C. Marshall, Ori D. Rotstein, Jun Peng, Ming Hou, Shinji Kunishima, Jerry Ware, Donald R. Branch, Alan H. Lazarus, Zaverio M. Ruggeri, John Freedman, Heyu Ni - Blood 2018 被引用: 79

platelets could not rescue impaired hepatic TPO production in vivo or in vitro, suggesting that GPIbα, independent of platelet desialylation, is a prerequisite for hepatic TPO generation. Additionally, impaired hepatic TPO production was recapitulated in interleukin-4/GPIbα-transgenic mice, as well as with antibodies targeting the extracellular portion of GPIbα, demonstrating that the N terminus of GPIbα is required for platelet-mediated hepatic TPO generation. These findings reveal a novel nonredundant regulatory role for platelets in hepatic TPO homeostasis, which improves our understanding of constitutive TPO regulation and has important implications in diseases related to GPIbα, such as BSS and auto- and alloimmune-mediated thrombocytopenias.