Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.
Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.
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DOI：
10.1371/journal.pone.0085530
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Pantopoulos K
中科院分区：
文献类型：
--
作者：
Gkouvatsos K;Fillebeen C;Daba A;Wagner J;Sebastiani G;Pantopoulos K
血幼素（Hemojuvelin，HSP 70）是一种骨形态发生蛋白（BMP）辅助受体，参与控制全身铁稳态。由于铁调节激素hepcidin的显著抑制，阻碍素的功能失活导致人类和小鼠中严重的铁过载。为了研究铁抑制剂在身体铁感应中的作用，将铁抑制剂−/−小鼠和同基因野生型对照置于适度低、标准或高铁饮食中四周。在所有方案下，HALF −/−小鼠均出现全身性铁超载。转铁蛋白（Tf）是高度饱和的，无论膳食铁含量，而肝脏铁沉积成正比。铁调素mRNA的表达响应膳食铁摄入量的波动，尽管没有阻碍。然而，铁调素的铁依赖性上调与野生型对照相比低一个数量级以上。同样，通过BMP/Smad途径的铁信号传导被保留，但基本上减弱。这些发现表明，HSP 70不是身体铁水平的传感所必需的，并且仅仅作为铁信号传导至铁调素的增强剂起作用。
Hemojuvelin (Hjv) is a bone morphogenetic protein (BMP) co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv−/− mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv−/− mice developed systemic iron overload under all regimens. Transferrin (Tf) was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.
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