IGF-1 facilitates thrombopoiesis primarily through Akt activation
IGF-1 facilitates thrombopoiesis primarily through Akt activation
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IGF-1 主要通过 Akt 激活促进血小板生成
DOI：
10.1182/blood-2018-01-825927
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发表时间：
2018-07-12
期刊：
影响因子：
20.3
通讯作者：
Wang, Junping
中科院分区：
文献类型：
--
作者：
Chen, Shilei;Hu, Mengjia;Wang, Junping
已知胰岛素样生长因子-1（IGF-1）也作为造血因子起作用，尽管其对血小板生成的直接作用尚不清楚。在这项研究中，我们表明，IGF-1能够促进CD 341细胞向巨核细胞（MK）分化，以及促进前血小板形成（PPF）和血小板从培养的MK生产。体内研究表明，IGF-1给药加速了6.0戈伊照射后的小鼠和10.0戈伊致死照射后接受骨髓移植的小鼠的血小板恢复。随后的研究表明，细胞外信号调节激酶1/2（ERK 1/2）和Akt激活介导的IGF-1对血小板生成的影响。值得注意的是，与血小板生成素（TPO）处理相比，IGF-1诱导的Akt活化比ERK 1/2更明显。此外，IGF-1对血小板生成的作用不依赖于TPO信号传导，因为IGF-1治疗也可导致纯合TPO受体突变小鼠中血小板计数的显著增加。进一步的分析表明，IGF-1激活Akt需要类固醇受体辅激活因子-3（SRC-3）的辅助。因此，我们的数据揭示了IGF-1在调节血小板生成中的独特作用，为TPO独立调节血小板生成提供了新的见解。
It is known that insulin-like growth factor-1 (IGF-1) also functions as a hematopoietic factor, although its direct effect on thrombopoiesis remains unclear. In this study, we show that IGF-1 is able to promote CD341 cell differentiation toward megakaryocytes (MKs), as well as the facilitation of proplatelet formation (PPF) and platelet production from cultured MKs. The in vivo study demonstrates that IGF-1 administration accelerates platelet recovery in mice after 6.0 Gy of irradiation and in mice that received bone marrow transplantation following 10.0 Gy of lethal irradiation. Subsequent investigations reveal that extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt activation mediate the effect of IGF-1 on thrombopoiesis. Notably, Akt activation induced by IGF-1 is more apparent than that of ERK1/2, compared with that of thrombopoietin (TPO) treatment. Moreover, the effect of IGF-1 on thrombopoiesis is independent of TPO signaling because IGF-1 treatment can also lead to a significant increase of platelet counts in homozygous TPO receptor mutant mice. Further analysis indicates that the activation of Akt triggered by IGF-1 requires the assistance of steroid receptor coactivator-3 (SRC-3). Therefore, our data reveal a distinct role of IGF-1 in regulating thrombopoiesis, providing new insights into TPO-independent regulation of platelet generation.