State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
Blood. 2018 Jul 12;132(2):210-222. doi: 10.1182/blood-2018-01-825927. Epub 2018 May 25.
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 CD34 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.
已知胰岛素样生长因子-1（IGF-1）也具有造血因子的功能，但其对巨核细胞生成（MK）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 CD34 细胞向巨核细胞（MK）分化，并促进原血小板形成（PPF）和培养的 MK 产生血小板。体内研究表明，IGF-1 给药可加速 6.0 Gy 照射后小鼠和 10.0 Gy 致死照射后接受骨髓移植的小鼠的血小板恢复。进一步的研究表明，细胞外信号调节激酶 1/2（ERK1/2）和 Akt 激活介导 IGF-1 对造血的影响。值得注意的是，与血小板生成素（TPO）处理相比，IGF-1 诱导的 Akt 激活比 ERK1/2 更为明显。此外，IGF-1 对造血的影响独立于 TPO 信号，因为 IGF-1 处理也可以导致纯合 TPO 受体突变小鼠的血小板计数显著增加。进一步的分析表明，IGF-1 触发的 Akt 激活需要类固醇受体共激活因子-3（SRC-3）的协助。因此，我们的数据揭示了 IGF-1 在调节造血中的独特作用，为 TPO 独立调节血小板生成提供了新的见解。
