Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation
Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation
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DOI：
10.1016/j.freeradbiomed.2019.03.023
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发表时间：
2019-05
影响因子：
7.4
通讯作者：
M. Yamaguchi;Tokuhisa Hirouchi;Haruhiko Yoshioka;J. Watanabe;I. Kashiwakura
中科院分区：
文献类型：
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作者：
M. Yamaguchi;Tokuhisa Hirouchi;Haruhiko Yoshioka;J. Watanabe;I. Kashiwakura
在发生放射性事故的情况下，特别是受害者受到高剂量电离辐射的情况下，给予适当的经批准的药品是最迅速的医疗。但目前还没有合适的人选。促血小板生成素受体（TPOR）激动剂romiplostim（RP）是一种免疫性血小板减少症的治疗药物，并有可能对这些受害者作出反应。在这里，我们表明，RP管理暴露于致死剂量辐射的小鼠不仅导致促进造血在多个器官，包括肺，但也减少了对器官和细胞的损害。RP还导致脾脏中间充质干细胞数量的快速增加。此外，RP抑制了参与辐射诱导的白血病发生的几种miRNA的表达，表明存在TPOR以外的靶点。在目前批准的药物中，RP是暴露于高剂量电离辐射的受害者的最合适的候选人。
In cases of radiological accidents, especially victims exposed to high-dose ionizing radiation, the administration of appropriate approved pharmaceutical drugs is the most rapid medical treatment. However, currently, there are no suitable candidates. The thrombopoietin receptor (TPOR) agonist romiplostim (RP) is a therapeutic agent for immune thrombocytopenia and has potential to respond to such victims. Here, we show that RP administration in mice exposed to lethal-dose radiation leads not only to the promotion of haematopoiesis in multiple organs, including the lungs but also a reduction in damage to organs and cells. RP also causes a rapid increase in the number of mesenchymal stem cells in the spleen. In addition, RP suppresses the expression of several miRNAs involved in radiation-induced leukemogenesis, suggesting the presence of targets other than TPOR. Among the currently approved pharmaceutical drugs, RP is the most suitable candidate for victims exposed to high-dose ionizing radiation.