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IGF-1 facilitates thrombopoiesis primarily through Akt activation

Shilei Chen, Mengjia Hu, Mingqiang Shen, Song Wang, Cheng Wang, Fang Chen, Yong Tang, Xinmiao Wang, Hao Zeng, Mo Chen, Jining Gao, Fengchao Wang, Yongping Su, Yang Xu and Junping Wang

Key Points

  • IGF-1 has the ability to promote megakaryocyte differentiation, PPF, and platelet release.

  • The effect of IGF-1 on thrombopoiesis is mediated primarily by AKT activation with the assistance of SRC-3.

Abstract

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.

  • Submitted January 29, 2018.
  • Accepted May 22, 2018.
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