Katsarou Angeliki, Pantopoulos Kostas
Lady Davis Institute for Medical Research, Jewish General Hospital, Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada.
Pharmaceuticals (Basel). 2018 Nov 21;11(4):127. doi: 10.3390/ph11040127.
Hepcidin is a key hormonal regulator of systemic iron homeostasis and its expression is induced by iron or inflammatory stimuli. Genetic defects in iron signaling to hepcidin lead to "hepcidinopathies" ranging from hereditary hemochromatosis to iron-refractory iron deficiency anemia, which are disorders caused by hepcidin deficiency or excess, respectively. Moreover, dysregulation of hepcidin is a pathogenic cofactor in iron-loading anemias with ineffective erythropoiesis and in anemia of inflammation. Experiments with preclinical animal models provided evidence that restoration of appropriate hepcidin levels can be used for the treatment of these conditions. This fueled the rapidly growing field of hepcidin therapeutics. Several hepcidin agonists and antagonists, as well as inducers and inhibitors of hepcidin expression have been identified to date. Some of them were further developed and are currently being evaluated in clinical trials. This review summarizes the state of the art.
铁调素是全身铁稳态的关键激素调节因子，其表达受铁或炎症刺激诱导。铁向铁调素信号传导的基因缺陷会导致“铁调素病”，从遗传性血色素沉着症到铁难治性缺铁性贫血，分别是由铁调素缺乏或过量引起的疾病。此外，铁调素失调是伴有无效红细胞生成的铁负荷性贫血和炎症性贫血的致病辅助因素。临床前动物模型实验提供了证据，表明恢复适当的铁调素水平可用于治疗这些病症。这推动了铁调素治疗学这一迅速发展的领域。迄今为止，已鉴定出几种铁调素激动剂和拮抗剂，以及铁调素表达的诱导剂和抑制剂。其中一些已得到进一步开发，目前正在临床试验中进行评估。本综述总结了最新进展。
