Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload
Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload
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DOI：
10.1172/jci25683
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发表时间：
2005-08-01
影响因子：
15.9
通讯作者：
Arber, S
中科院分区：
文献类型：
--
作者：
Niederkofler, V;Salie, R;Arber, S
铁稳态在许多生理过程中起着关键作用，特别是血红素蛋白的合成。膳食铁感应和炎症通过调节铁调素（铁转运蛋白的调节剂）的表达来控制铁的吸收和保留。人类突变的糖基磷脂酰肌醇锚定蛋白hemojuvelin（HJV;也称为RGMc和HFE 2）导致青少年血色素沉着症，一种严重的铁超载疾病，但HJV与铁调控网络的交叉方式尚不清楚。在这里，我们表明，在肝脏内，小鼠HHV门静脉周围肝细胞选择性表达，HHV突变小鼠表现出铁过载以及铁调素表达的显着减少。我们的研究结果定义了Hjv在膳食铁传感中的关键作用，并揭示了Hjv诱导的炎症通过Hjv独立途径调节hepcidin表达。
Iron homeostasis plays a critical role in many physiological processes, notably synthesis of heme proteins. Dietary iron sensing and inflammation converge in the control of iron absorption and retention by regulating the expression of hepcidin, a regulator of the iron exporter ferroportin. Human mutations in the glycosylphosphatidylinositol-anchored protein hemojuvelin (HJV; also known as RGMc and HFE2) cause juvenile hemochromatosis, a severe iron overload disease, but the way in which HJV intersects with the iron regulatory network has been unclear. Here we show that, within the liver, mouse Hjv is selectively expressed by periportal hepatocytes and also that Hjv-mutant mice exhibit iron overload as well as a dramatic decrease in hepcidin expression. Our findings define a key role for Hjv in dietary iron sensing and also reveal that cytokine-induced inflammation regulates hepcidin expression through an Hjv-independent pathway.