Iron-refractory iron deficiency anemia: new molecular mechanisms.
Iron-refractory iron deficiency anemia: new molecular mechanisms.
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DOI：
10.1038/ki.2009.357
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发表时间：
2009-12
影响因子：
19.6
通讯作者：
Zhou, Yiqing
中科院分区：
文献类型：
--
作者：
Cui, Yujie;Wu, Qingyu;Zhou, Yiqing
缺铁是贫血的常见原因。在终末期肾病（ESRD）中，缺铁损害重组红细胞生成素的治疗效果。口服或父母铁补充剂通常是有效的治疗缺铁性贫血（IDA）。然而，一些患者对铁补充剂反应不佳，被诊断为铁难治性缺铁性贫血（IRIDA）。这种疾病是一种医学挑战，但其潜在机制尚不清楚。Hepcidin在铁稳态中起核心作用。它下调铁出口蛋白铁转运蛋白，从而抑制铁的吸收、释放和再循环。ESRD患者血浆hepcidin水平升高，导致患者缺铁。matpase -2是一种肝脏跨膜丝氨酸蛋白酶，已被发现在控制hepcidin基因表达中起重要作用。在小鼠中，编码基质酶-2的Tmprss6基因缺陷导致hepcidin高表达，导致严重的小细胞性贫血。同样，在IRIDA患者中也发现了人类TMPRSS6基因的突变。因此，基质蛋白酶-2对铁稳态至关重要，并可能在肾脏疾病中发挥作用。
Iron deficiency is a common cause of anemia. In end-stage renal disease (ESRD), iron deficiency impairs the therapeutic efficacy of recombinant erythropoietin. Oral or parental iron supplements usually are effective in treating iron deficiency anemia (IDA). Some patients, however, respond poorly to iron supplements and are diagnosed as having iron-refractory iron deficiency anemia (IRIDA). The disease represents a medical challenge but its underlying mechanism was unclear. Hepcidin is a central player in iron homeostasis. It down-regulates the iron exporter ferroportin, thereby inhibiting iron absorption, release and recycling. In ESRD, plasma hepcidin levels are elevated, which contributes to iron deficiency in patients. Matriptase-2, a liver transmembrane serine protease, has been found to have a major role in controlling hepcidin gene expression. In mice, defects in the Tmprss6 gene encoding matriptase-2 result in high hepcidin expression and cause severe microcytic anemia. Similarly, mutations in the human TMPRSS6 gene have been identified in patients with IRIDA. Thus, matriptase-2 is critical for iron homeostasis and may play a role in renal disease.
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