Thrombopoiesis promoted by IGF-1 requires the involvement of SRC-3. (A-B) Peripheral platelet counts (A) and serum IGF-1 levels (B) in SRC-3^−/− mice or WT mice. (C) Peripheral platelet counts in WT C57BL/6 mice that were injected intraperitoneally with NVP-ADW742 (10 mg/kg i.p. twice daily) for 7 days. (D) Fold increase of peripheral platelet counts in WT or SRC-3^−/− mice injected with saline or rhIGF-1 for 7 days. (E-F) Proplatelet-forming cells (E) and culture-derived platelets (F) from mouse-derived MKs cultured with or without rhIGF-1 for 3 days. Mouse-derived MKs were cultured from SRC-3^−/− or WT c-kit⁺ cells stimulated with rhTPO for 5 days in the presence of 10 ng/mL rmIL-3. (G) Association between IGF-1R and IRS-1or IRS-2 in mouse-derived MKs from SRC-3^−/− or WT mice after treatment with 100 ng/mL rhIGF-1. Lysates were subjected to immunoprecipitation with antibody against IGF-1R and were immunoblotted with antibodies against p-Tyr, IRS-1, IRS-2, or IGF-1R. (H-I) western blot analysis of the activation of ERK1/2 and Akt signal pathways in mouse-derived MKs after exposure to rhIGF-1 or rhTPO for 15 minutes. (J) Schematic illustration of the role of IGF-1 in thrombopoiesis. IGF-1 mainly acts through ERK1/2 and Akt, especially via the Akt signal pathway, thereby facilitating thrombopoiesis. Notably, this promotion is more than a result of working through TPO signaling, and requires the assistance of SRC-3. *P < .05, **P < .01.