Arcasoy Murat O
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Br J Haematol. 2008 Apr;141(1):14-31. doi: 10.1111/j.1365-2141.2008.07014.x.
In the haematopoietic system, the principal function of erythropoietin (Epo) is the regulation of red blood cell production, mediated by its specific cell surface receptor (EpoR). Following the cloning of the Epo gene (EPO) and characterization of the selective haematopoietic action of Epo in erythroid lineage cells, recombinant Epo forms (epoetin-alfa, epoetin-beta and the long-acting analogue darbepoetin-alfa) have been widely used for treatment of anaemia in chronic kidney disease and chemotherapy-induced anaemia in cancer patients. Ubiquitous EpoR expression in non-erythroid cells has been associated with the discovery of diverse biological functions for Epo in non-haematopoietic tissues. During development, Epo-EpoR signalling is required not only for fetal liver erythropoiesis, but also for embryonic angiogenesis and brain development. A series of recent studies suggest that endogenous Epo-EpoR signalling contributes to wound healing responses, physiological and pathological angiogenesis, and the body's innate response to injury in the brain and heart. Epo and its novel derivatives have emerged as major tissue-protective cytokines that are being investigated in the first human studies involving neurological and cardiovascular diseases. This review focuses on the scientific evidence documenting the biological effects of Epo in non-haematopoietic tissues and discusses potential future applications of Epo and its derivatives in the clinic.
在造血系统中，促红细胞生成素（Epo）的主要功能是通过其特异性细胞表面受体（EpoR）介导来调节红细胞生成。在促红细胞生成素基因（EPO）克隆成功以及其在红系谱系细胞中选择性造血作用的特性被阐明之后，重组促红细胞生成素形式（阿法依泊汀、贝他依泊汀以及长效类似物达贝泊汀-α）已被广泛用于治疗慢性肾脏病贫血以及癌症患者化疗所致的贫血。非红系细胞中普遍存在的促红细胞生成素受体（EpoR）表达与促红细胞生成素在非造血组织中的多种生物学功能的发现有关。在发育过程中，促红细胞生成素-促红细胞生成素受体信号传导不仅是胎儿肝脏红细胞生成所必需的，也是胚胎血管生成和脑发育所必需的。最近的一系列研究表明，内源性促红细胞生成素-促红细胞生成素受体信号传导有助于伤口愈合反应、生理性和病理性血管生成以及机体对脑和心脏损伤的固有反应。促红细胞生成素及其新型衍生物已成为主要的组织保护细胞因子，目前正在涉及神经和心血管疾病的首批人体研究中进行调查。本综述重点关注记录促红细胞生成素在非造血组织中生物学效应的科学证据，并讨论促红细胞生成素及其衍生物在临床上潜在的未来应用。
