Transferrin therapy ameliorates disease in β-thalassemic mice
Transferrin therapy ameliorates disease in β-thalassemic mice
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DOI：
10.1038/nm.2073
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发表时间：
2010-02-01
期刊：
影响因子：
82.9
通讯作者：
Ginzburg, Yelena Z.
中科院分区：
文献类型：
--
作者：
Li, Huihui;Rybicki, Anne C.;Ginzburg, Yelena Z.
β-地中海贫血患者会发生进行性全身性铁超载，导致高发病率和死亡率。这些并发症是由不稳定的血浆铁引起的，其以失调的方式被实质细胞摄取;相反，红细胞生成依赖于通过转铁蛋白受体的转铁蛋白结合铁摄取。我们推测，在β地中海贫血中观察到的无效红细胞生成和贫血可能通过增加循环转铁蛋白的量而得到改善。我们测试了转铁蛋白注射液调节Hbb（th 1/th 1）小鼠（β-地中海贫血的实验模型）铁代谢和红细胞生成的能力。注射转铁蛋白逆转或显着改善这些小鼠的地中海贫血表型。具体而言，转铁蛋白注射使不稳定的血浆铁浓度正常化，增加铁调素表达，使红细胞存活正常化并增加血红蛋白产生;这种治疗伴随着减少网织红细胞增多症，促红细胞生成素丰度和脾肿大。这些结果表明，转铁蛋白是导致这些小鼠贫血的限制因素，并表明转铁蛋白治疗可能对人类β地中海贫血有益。
Individuals with beta-thalassemia develop progressive systemic iron overload, resulting in high morbidity and mortality. These complications are caused by labile plasma iron, which is taken up by parenchymal cells in a dysregulated manner; in contrast, erythropoiesis depends on transferrin-bound iron uptake via the transferrin receptor. We hypothesized that the ineffective erythropoiesis and anemia observed in beta-thalassemia might be ameliorated by increasing the amount of circulating transferrin. We tested the ability of transferrin injections to modulate iron metabolism and erythropoiesis in Hbb(th1/th1) mice, an experimental model of beta-thalassemia. Injected transferrin reversed or markedly improved the thalassemia phenotype in these mice. Specifically, transferrin injections normalized labile plasma iron concentrations, increased hepcidin expression, normalized red blood cell survival and increased hemoglobin production; this treatment concomitantly decreased reticulocytosis, erythropoietin abundance and splenomegaly. These results indicate that transferrin is a limiting factor contributing to anemia in these mice and suggest that transferrin therapy might be beneficial in human beta-thalassemia.