Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Biochem Pharmacol. 2011 Nov 15;82(10):1291-303. doi: 10.1016/j.bcp.2011.06.045. Epub 2011 Jul 7.
Erythropoietin (EPO) is a glycoprotein that is mainly produced in the adult kidney, and it was initially highlighted for its action on the hematopoietic system. Moreover, EPO is also expressed in several non-hematopoietic tissues, where it plays a role in the protection from apoptosis and inflammation due to hypoxia, toxicity or injury. These protective effects are mainly known and studied in cardioprotection and neuroprotection but are also reported in retina degeneration, auditory injury and pancreatic-related diseases. The tissue protective effect of EPO is mainly mediated through the interaction with the heterodimeric receptor EPOR/βcR. Human recombinant EPO (HuREPO), which has been developed to treat anemia, is not adequate for tissue protection. The low affinity of the alternative receptor for EPO involves the injection of excessive concentration of erythropoiesis-stimulating agents (ESAs), implicating side effects due to the cross-talk with hematopoietic activity. For these reasons, EPO derivatives with less affinity for the EPO homodimeric receptor are under development. In this review, we provide an overview of the erythroid and non-erythroid functions of EPO by detailing the molecular mechanisms activated by the binding of EPO to its receptors in different tissues.
促红细胞生成素（EPO）是一种糖蛋白，主要在成人肾脏中产生，最初因其对造血系统的作用而受到关注。此外，EPO 也在几种非造血组织中表达，在这些组织中，它在缺氧、毒性或损伤引起的细胞凋亡和炎症中发挥作用。这些保护作用主要在心脏保护和神经保护中得到了解和研究，但也在视网膜变性、听觉损伤和胰腺相关疾病中得到了报道。EPO 的组织保护作用主要通过与异二聚体受体 EPOR/βcR 的相互作用来介导。为治疗贫血而开发的人重组促红细胞生成素（HuREPO）不足以用于组织保护。EPO 的替代受体的低亲和力涉及到注射过多浓度的促红细胞生成素刺激剂（ESAs），这意味着由于与造血活性的交叉作用而产生副作用。出于这些原因，正在开发对 EPO 同源二聚体受体亲和力较低的 EPO 衍生物。在这篇综述中，我们通过详细描述 EPO 与其受体结合在不同组织中激活的分子机制，概述了 EPO 的红系和非红系功能。
