Center of Excellence in Stem Cell Biology and Regenerative Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA.
Curr Opin Hematol. 2010 May;17(3):169-76. doi: 10.1097/MOH.0b013e328338008b.
In 1985-1989, erythropoietin (EPO), its receptor (EPOR), and janus kinase 2 were cloned; established to be essential for definitive erythropoiesis; and initially intensely studied. Recently, new impetus, tools, and model systems have emerged to re-examine EPO/EPOR actions, and are addressed in this review. Impetus includes indications that EPO affects significantly more than standard erythroblast survival pathways, the development of novel erythropoiesis-stimulating agents, increasing evidence for EPO/EPOR cytoprotection of ischemically injured tissues, and potential EPO-mediated worsening of tumorigenesis.
New findings are reviewed in four functional contexts: (pro)erythroblast survival mechanisms, new candidate EPO/EPOR effects on erythroid cell development and new EPOR responses, EPOR downmodulation and trafficking, and novel erythropoiesis-stimulating agents.
As Current Opinion, this monograph seeks to summarize, and provoke, new EPO/EPOR action concepts. Specific problems addressed include: beyond (and before) BCL-XL, what key survival factors are deployed in early-stage proerythroblasts? Are distinct EPO/EPOR signals transduced in stage-selective fashions? Is erythroblast proliferation also modulated by EPO/EPOR signals? What functions are subserved by new noncanonical EPO/EPOR response factors (e.g. podocalyxin like-1, tribbles 3, reactive oxygen species, and nuclear factor kappa B)? What key regulators mediate EPOR inhibition and trafficking? And for emerging erythropoiesis-stimulating agents, to what extent do activities parallel EPOs (or differ in advantageous, potentially complicating ways, or both)?
1985-1989 年，促红细胞生成素（EPO）、其受体（EPOR）和 Janus 激酶 2 被克隆；被确定对确定的红细胞生成至关重要；并最初进行了深入研究。最近，出现了新的动力、工具和模型系统来重新检查 EPO/EPOR 的作用，本综述对此进行了讨论。动力包括以下迹象：EPO 不仅显著影响标准红细胞生存途径，还影响新型红细胞生成刺激剂的发展，越来越多的证据表明 EPO/EPOR 对缺血性损伤组织具有细胞保护作用，以及潜在的 EPO 介导的肿瘤恶化作用。
在四个功能背景下审查了新的发现：（前）红细胞生成细胞的生存机制、EPO/EPOR 对红细胞生成细胞发育和新的 EPOR 反应的新候选作用、EPOR 下调和运输、以及新型红细胞生成刺激剂。
作为本期《Current Opinion》，本专论旨在总结和引发 EPO/EPOR 作用的新概念。具体解决的问题包括：除了（和之前）BCL-XL 之外，早期前红细胞生成细胞中还部署了哪些关键生存因子？是否以阶段选择性方式转导不同的 EPO/EPOR 信号？EPO/EPOR 信号是否也调节红细胞生成细胞的增殖？新的非典型 EPO/EPOR 反应因子（例如足细胞样蛋白 1、Tribbles 3、活性氧和核因子 kappa B）发挥什么功能？哪些关键调节剂介导 EPOR 抑制和运输？对于新兴的红细胞生成刺激剂，其活性在多大程度上与 EPO 相似（或在有利的、潜在复杂的方面不同，或两者兼有）？
