Regulation of erythropoiesis by hypoxia-inducible factors.
Regulation of erythropoiesis by hypoxia-inducible factors.
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DOI：
10.1016/j.blre.2012.12.003
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发表时间：
2013-01
期刊：
影响因子：
7.4
通讯作者：
Haase VH
中科院分区：
文献类型：
--
作者：
Haase VH
对全身缺氧的典型生理反应是红细胞生成的增加。缺氧诱导因子（HIF）通过诱导细胞类型特异性基因表达变化来协调这种反应，从而增加肾脏和肝脏中促红细胞生成素（EPO）的产生，增强铁的吸收和利用，并调整骨髓微环境，促进红系祖细胞的成熟和增殖。特别是 HIF-2 已成为调节肾脏和肝脏中 EPO 合成的转录因子，并在调节肠道铁吸收中发挥关键作用。对生活在高海拔地区的人群进行的遗传学研究以及对家族性红细胞增多症患者的突变分析强调了其在红细胞生成的缺氧调节中的关键功能。这篇综述提供了对 HIF 控制的红细胞生成和铁代谢的最新见解的视角，并检查了具有 EPO 生成能力的细胞类型。此外，该综述还总结了与氧气感应途径突变相关的临床综合征以及高海拔地区居民发生的基因变化。讨论了药理学 HIF 激活治疗贫血的治疗潜力。
A classic physiologic response to systemic hypoxia is the increase in red blood cell production. Hypoxia-inducible factors (HIFs) orchestrate this response by inducing cell-type specific gene expression changes that result in increased erythropoietin (EPO) production in kidney and liver, in enhanced iron uptake and utilization and in adjustments of the bone marrow microenvironment that facilitate erythroid progenitor maturation and proliferation. In particular HIF-2 has emerged as the transcription factor that regulates EPO synthesis in the kidney and liver and plays a critical role in the regulation of intestinal iron uptake. Its key function in the hypoxic regulation of erythropoiesis is underscored by genetic studies in human populations that live at high-altitude and by mutational analysis of patients with familial erythrocytosis. This review provides a perspective on recent insights into HIF-controlled erythropoiesis and iron metabolism, and examines cell types that have EPO-producing capability. Furthermore, the review summarizes clinical syndromes associated with mutations in the O2-sensing pathway and the genetic changes that occur in high altitude natives. The therapeutic potential of pharmacologic HIF activation for the treatment of anemia is discussed.
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影响因子：
13.6
作者：
Babitt, Jodie L.;Lin, Herbert Y.
通讯作者：
Lin, Herbert Y.
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang
影响因子：
5.3
作者：
BLANCHARD, KL;ACQUAVIVA, AM;BUNN, HF
通讯作者：
BUNN, HF
影响因子：
11.2
作者：
Aprelikova, Olga;Wood, Matthew;Barrett, J. Carl
通讯作者：
Barrett, J. Carl
影响因子：
2.3
作者：
Al-Sheikh, Maha;Moradkhani, Kamran;Prehu, Claude
通讯作者：
Prehu, Claude