@article{Jie Yu Ye_Godfrey Chi Fung Chan_Liang Qiao_Qizhou Lian_Fan Yi Meng_Xue Qun Luo_Levon M. Khachigian_Ming Ma_Ruixia Deng_Jian Liang Chen_Beng H. Chong_Mo Yang_2010, place={Pavia, Italy}, title={Platelet-derived growth factor enhances platelet recovery in a murine model of radiation-induced thrombocytopenia and reduces apoptosis in megakaryocytes via its receptors and the PI3-k/Akt pathway}, volume={95}, url={https://haematologica.org/article/view/5760}, DOI={10.3324/haematol.2009.020958}, abstractNote={<strong>Background</strong> Platelet-derived growth factor is involved in the regulation of hematopoiesis. Imatinib mesylate, a platelet-derived growth factor receptor inhibitor, induces thrombocytopenia in a significant proportion of patients with chronic myeloid leukemia. Although our previous studies showed that platelet-derived growth factor enhances megakaryocytopoiesis <em>in vitro</em>, the <em>in vivo</em> effect of platelet-derived growth factor in a model of radiation-induced thrombocytopenia has not been reported.<strong>Design and Methods</strong> In this study, we investigated the effect of platelet-derived growth factor on hematopoietic stem/progenitor cells and platelet production using an irradiated-mouse model. We also explored the potential molecular mechanisms of platelet-derived growth factor on thrombopoiesis in M-07e cells.<strong>Results</strong> Platelet-derived growth factor, like thrombopoietin, significantly promoted the recovery of platelets and the formation of bone marrow colony-forming unit-megakaryocyte in irradiated mice. Histology confirmed the protective effect of platelet-derived growth factor, as shown by an increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis. In a megakaryocytic apoptotic model, platelet-derived growth factor had a similar anti-apoptotic effect as thrombopoietin on megakaryocytes. We also demonstrated that platelet-derived growth factor activated the PI3-k/Akt signaling pathway, while addition of imatinib mesylate reduced p-Akt expression.<strong>Conclusions</strong&gt; Our findings show that platelet-derived growth factor enhances platelet recovery in mice with radiation-induced thrombocytopenia. This radioprotective effect is likely to be mediated via platelet-derived growth factor receptors with subsequent activation of the PI3-k/Akt pathway. We also provide a possible explanation that blockage of platelet-derived growth factor receptors may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia.}, number={10}, journal={Haematologica}, author={Jie Yu Ye and Godfrey Chi Fung Chan and Liang Qiao and Qizhou Lian and Fan Yi Meng and Xue Qun Luo and Levon M. Khachigian and Ming Ma and Ruixia Deng and Jian Liang Chen and Beng H. Chong and Mo Yang}, year={2010}, month={Sep.}, pages={1745-1753} }