mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease.
mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease.
复制标题
mTOR 抑制可改善镰状细胞病小鼠模型中的贫血并减少器官损伤。
DOI：
10.1111/bjh.14057
复制
发表时间：
2016
影响因子：
6.5
通讯作者：
Eitzman,DanielT
中科院分区：
文献类型：
--
作者：
Wang,Jintao;Tran,Jennifer;Wang,Hui;Guo,Chiao;Harro,David;Campbell,AndrewD;Eitzman,DanielT
Mechanistic target of rapamycin (mTOR) has been shown to play an important role in red blood cell physiology, with inhibition of mTOR signalling leading to alterations in erythropoiesis. To determine if mTOR inhibition would improve anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual mTORC1/2 inhibitor, INK128. One week after daily oral drug treatment, erythrocyte count, haemoglobin, and haematocrit were all significantly increased while reticulocyte counts were reduced. These parameters remained stable during 3 weeks of treatment. Similar effects were observed following oral treatment with the mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle cell erythrocytes in circulation, reduced spleen size, and reduced renal and hepatic iron accumulation in SCD mice. Following middle cerebral artery occlusion, stroke size was reduced in SCD mice treated with sirolimus. In conclusion, mTOR inhibition is protective against anaemia and organ damage in a murine model of SCD.
