Function of hemojuvelin in the heart and skeletal muscles

哺乳动物饮食中铁的吸收和体内铁的运输受肝源性多肽激素海普西丁的控制。海普西丁与靶细胞中铁出口蛋白铁蛋白结合，促进其降解，从而抑制进入血流的铁通量。海普西丁的表达需要血凝素(hemjuvelin，Hjv)，一种骨形态发生蛋白(BMP)的共同受体。HJV通过增强铁依赖的BMP/SMAD信号转导肝脏中的海普西丁来发挥作用，肝脏是海普西丁产生的主要部位。肝脏特异性干扰海普西丁或Hjv会导致严重的铁超载。海普西丁和Hjv在其他组织中也有表达，在这些组织中它们可能发挥局部功能。HJV在心脏和骨骼肌中含量非常丰富。通过产生肝脏和肌肉特异的Hjv-/-小鼠，我们证明只有肝脏Hjv调节全身铁稳态。

Mammalian dietary iron absorption and body iron traffic are controlled by hepcidin, a liver-derived peptide hormone. Hepcidin binds to the iron exporter ferroportin in target cells and promotes its degradation, thereby inhibiting iron flux into the bloodstream. The expression of hepcidin requires hemojuvelin (Hjv), a bone morphogenetic protein (BMP) co-receptor. Hjv operates by enhancing iron-dependent BMP/SMAD signaling to hepcidin in the liver, the major site of hepcidin production. Liver-specific disruption of either hepcidin or Hjv leads to severe iron overload. Both hepcidin and Hjv are also expressed in other tissues, where they may exert localized functions. Hjv is highly abundant in the heart and skeletal muscles. By generating liver- and muscle-specific Hjv-/- mice, we demonstrated that only liver Hjv regulates systemic iron homeostasis.