The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation
The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation
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DOI：
10.1172/jci200215686
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发表时间：
2002-10-01
影响因子：
15.9
通讯作者：
Vaulont, S
中科院分区：
文献类型：
--
作者：
Nicolas, G;Chauvet, C;Vaulont, S
本研究旨在确定铁调素（一种最近发现的参与铁代谢的肽）是否在与铁超载和铁缺乏相关的疾病中发挥作用。在两种贫血模型（苯肼引起的急性溶血和反复放血引起的出血）中评估了铁调素 mRNA 水平。还研究了铁调素对缺氧的反应，包括离体、人肝癌细胞和体内。贫血和缺氧与肝脏铁调素基因表达的急剧下降有关，这可能是这些情况下经常观察到的网状内皮细胞铁释放增加和铁吸收增加的原因。单次注射松节油 16 小时，可使肝脏铁调素 mRNA 水平增加六倍，血清铁减少两倍。在铁调素缺乏的小鼠中，松节油的降血脂作用完全减弱，这表明铁调素参与了炎症状态的贫血。铁调素基因表达的这些修饰进一步表明铁调素在各种病理生理条件下铁稳态中的关键作用，这可能支持铁调素激动剂和拮抗剂在各种铁稳态紊乱中的药物用途。
The present study was aimed at determining whether hepcidin, a recently identified peptide involved in iron metabolism, plays a role in conditions associated with both iron overload and iron deficiency. Hepcidin mRNA levels were assessed in two models of anemia, acute hemolysis provoked by phenylhydrazine and bleeding provoked by repeated phlebotomies. Hepcidin response to hypoxia was also studied, both ex vivo, in human hepatoma cells, and in vivo. Anemia and hypoxia were associated with a dramatic decrease in liver hepcidin gene expression, which may account for the increase in iron release from reticuloendothelial cells and increase in iron absorption frequently observed in these situations. A single injection of turpentine for 16 hours induced a sixfold increase in liver hepcidin mRNA levels and a twofold decrease in serum iron. The hyposideremic effect of turpentine was completely blunted in hepcidin-deficient mice, revealing hepcidin participation in anemia of inflammatory states. These modifications of hepcidin gene expression further suggest a key role for hepcidin in iron homeostasis under various pathophysiological conditions, which may support the pharmaceutical use of hepcidin agonists and antagonists in various iron homeostasis disorders.