Division of Genetics and Cell Biology, San Raffaele Scientific Institute and Vita Salute University, Milano, Italy.
Br J Haematol. 2018 Aug;182(4):481-494. doi: 10.1111/bjh.15403. Epub 2018 Jun 25.
Recent years have witnessed impressive advances in our understanding of iron metabolism. A number of studies of iron disorders and of their animal models have provided landmark insights into the mechanisms of iron trafficking, distribution and homeostatic regulation, the latter essential to prevent both iron deficiency and iron excess. Our perception of iron metabolism has been completely changed by an improved definition of cellular and systemic iron homeostasis, of the molecular pathogenesis of iron disorders, the fine tuning of the iron hormone hepcidin by activators and inhibitors and the dissection of the components of the hepcidin regulatory pathway. Important for haematology, the crosstalk of erythropoiesis, the most important iron consumer, and the hepcidin pathway has been at least partially clarified. Novel potential biomarkers are available and novel therapeutic targets for iron-related disorders have been tested in murine models. These preclinical studies provided proofs of principle and are laying the ground for clinical trials. Understanding iron control in tissues other than erythropoiesis remains a challenge for the future.
近年来,我们对铁代谢的理解取得了令人瞩目的进展。许多关于铁代谢紊乱及其动物模型的研究为铁运输、分布和体内平衡调节的机制提供了里程碑式的见解,而后者对于预防铁缺乏和铁过载至关重要。通过对细胞和系统铁稳态、铁代谢紊乱的分子发病机制、铁激素铁调素的激活剂和抑制剂的精细调节以及铁调素调控途径的组成部分的解析,我们对铁代谢的认识发生了彻底的改变。对血液学来说,最重要的铁消耗者——红细胞生成和铁调素途径之间的相互作用至少部分得到了阐明。目前已有新的潜在生物标志物,并在小鼠模型中对与铁相关的疾病的新治疗靶点进行了测试。这些临床前研究提供了原理性的证据,并为临床试验奠定了基础。了解除红细胞生成以外的组织中的铁控制仍然是未来的一个挑战。