Anaemia in kidney disease: harnessing hypoxia responses for therapy.
Anaemia in kidney disease: harnessing hypoxia responses for therapy.
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DOI：
10.1038/nrneph.2015.82
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发表时间：
2015-07
影响因子：
41.5
通讯作者：
Haase, Volker H.
中科院分区：
文献类型：
--
作者：
Koury, Mark J.;Haase, Volker H.
对红细胞生成的氧依赖性调节的更好理解为与肾衰竭相关的贫血的发病机制提供了新的见解，并导致了用于其治疗的新型治疗剂的开发。缺氧诱导因子（HIF）-2是红细胞生成和铁代谢的关键调节因子。HIF-2在缺氧条件下被激活，并控制肾小管周围间质成纤维细胞样细胞和肝细胞产生促红细胞生成素。在与肾脏疾病相关的贫血中，红细胞生成由于肾脏中红细胞生成素产生不足、炎症和铁缺乏而受到抑制;然而，激活HIF轴的药理学药物可以通过模拟协调红细胞生成与铁代谢的缺氧反应来提供治疗肾性贫血的生理方法。本文综述了促红细胞生成素、铁和炎症介质在生理条件下的功能相互关系，以及与肾性贫血发病机制的关系，并对促红细胞生成素在肾脏产生的分子和细胞基础进行了综述。它还提供了一个详细的概述，目前的临床经验与HIF信号的药理学激活剂作为一种新的全面和生理的方法来治疗贫血。
Improved understanding of the oxygen-dependent regulation of erythropoiesis has provided new insights into the pathogenesis of anaemia associated with renal failure and has led to the development of novel therapeutic agents for its treatment. Hypoxia-inducible factor (HIF)-2 is a key regulator of erythropoiesis and iron metabolism. HIF-2 is activated by hypoxic conditions and controls the production of erythropoietin by renal peritubular interstitial fibroblast-like cells and hepatocytes. In anaemia associated with renal disease, erythropoiesis is suppressed due to inadequate erythropoietin production in the kidney, inflammation and iron deficiency; however, pharmacologic agents that activate the HIF axis could provide a physiologic approach to the treatment of renal anaemia by mimicking hypoxia responses that coordinate erythropoiesis with iron metabolism. This Review discusses the functional inter-relationships between erythropoietin, iron and inflammatory mediators under physiologic conditions and in relation to the pathogenesis of renal anaemia, as well as recent insights into the molecular and cellular basis of erythropoietin production in the kidney. It furthermore provides a detailed overview of current clinical experience with pharmacologic activators of HIF signalling as a novel comprehensive and physiologic approach to the treatment of anaemia.
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影响因子：
29
作者：
Anderson SA;Nizzi CP;Chang YI;Deck KM;Schmidt PJ;Galy B;Damnernsawad A;Broman AT;Kendziorski C;Hentze MW;Fleming MD;Zhang J;Eisenstein RS
通讯作者：
Eisenstein RS
影响因子：
9.6
作者：
Baillie, J. Kenneth;Bates, Matthew G. D.;Webb, David J.
通讯作者：
Webb, David J.
影响因子：
4.8
作者：
Bodo, Eniko;Kromminga, Arno;Paus, Ralf
通讯作者：
Paus, Ralf
影响因子：
10.5
作者：
Bauer, A;Tronche, F;Beug, H
通讯作者：
Beug, H
影响因子：
56.9
作者：
Bruick, RK;McKnight, SL
通讯作者：
McKnight, SL