Department Endocrinology Metabolism and Diabetes, INSERM U1016, Institut Cochin.
CNRS, UMR8104.
Curr Opin Hematol. 2019 May;26(3):125-130. doi: 10.1097/MOH.0000000000000494.
This review outlines recent discoveries on the crosstalk between oxygen metabolism and iron homeostasis, focusing on the role of HIF-2 (hypoxia inducible factor-2) in the regulation of iron metabolism under physiopathological conditions.
The importance of the hepcidin/ferroportin axis in the modulation of intestinal HIF-2 to regulate iron absorption has been recently highlighted. Latest advances also reveal a direct titration of the bone morphogenetic proteins by the erythroferrone contributing to liver hepcidin suppression to increase iron availability. Iron is recycled thanks to erythrophagocytosis of senescent erythrocytes by macrophages. Hemolysis is frequent in sickle cell anemia, leading to increased erythrophagocytosis responsible of the macrophage polarization shift. New findings assessed the effects of hemolysis on macrophage polarization in the tumor microenvironment.
Hypoxia signaling links erythropoiesis with iron homeostasis. The use of HIF stabilizing or inhibiting drugs are promising therapeutic approaches in iron-associated diseases.
本文概述了氧代谢与铁稳态之间相互作用的最新发现，重点介绍了低氧诱导因子 2（HIF-2）在生理病理条件下调节铁代谢中的作用。
最近强调了血红素/亚铁转运蛋白轴在调节肠道 HIF-2 以调节铁吸收中的重要性。最新进展还揭示了红细胞生成素通过直接滴定骨形态发生蛋白有助于抑制肝脏中的铁调素，从而增加铁的可用性。铁通过巨噬细胞吞噬衰老的红细胞进行回收。镰状细胞贫血症中常发生溶血，导致吞噬作用增加，从而导致巨噬细胞极化转变。新的发现评估了溶血对肿瘤微环境中巨噬细胞极化的影响。
缺氧信号通路将红细胞生成与铁稳态联系起来。使用 HIF 稳定剂或抑制剂药物是治疗铁相关疾病的有前途的方法。
