Hepcidin is the master regulator of systemic iron homeostasis, facilitating iron balance by controlling intestinal iron absorption and recycling. Hepcidin levels are suppressed when erythropoiesis is stimulated, for example following acute blood loss, appropriately enhancing cellular iron export to the plasma to support production of new red blood cells. However, persistent increased and ineffective erythropoiesis, for example in thalassemia, results in sustained elevations in iron absorption, which cause iron overload with associated organ toxicities. The ligands, receptors, and canonical pathways by which iron loading and inflammation upregulate hepcidin expression have been largely established. However, although several mechanisms have been proposed, the means by which erythropoiesis causes hepcidin suppression have been unclear. The erythroid-derived hormone erythroferrone appears to be a convincing candidate for the link between increased erythropoiesis and hepcidin suppression. If confirmed to be clinically and physiologically relevant in humans, potentiation or inhibition of erythroferrone activity could be a crucial pharmaceutical strategy.

中文翻译：

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红细胞生成对铁调素的调节：迄今为止的故事。

铁调素是全身铁稳态的主要调节剂，通过控制肠道铁的吸收和循环来促进铁平衡。当刺激红细胞生成时，例如在急性失血后，铁调素水平会受到抑制，适当地增强细胞铁向血浆的输出以支持新红细胞的产生。然而，持续增加和无效的红细胞生成，例如在地中海贫血中，会导致铁吸收持续升高，从而导致铁超负荷和相关的器官毒性。铁负荷和炎症上调铁调素表达的配体、受体和经典途径已基本确立。然而，尽管已经提出了几种机制，但红细胞生成导致铁调素抑制的方式尚不清楚。红细胞衍生激素 erythroferrone 似乎是红细胞生成增加与铁调素抑制之间联系的令人信服的候选者。如果证实在人类中具有临床和生理相关性，那么增强或抑制赤铁酮活性可能是一种关键的药物策略。