ISOLATION AND CHARACTERIZATION OF GENOMIC AND CDNA CLONES OF HUMAN ERYTHROPOIETIN

ISOLATION AND CHARACTERIZATION OF GENOMIC AND CDNA CLONES OF HUMAN ERYTHROPOIETIN
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DOI:
10.1038/313806a0
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发表时间:
1985-01-01
期刊:
影响因子:
64.8
通讯作者:
MIYAKE, T
MIYAKE, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
JACOBS, K;SHOEMAKER, C;MIYAKE, T

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糖蛋白激素促红细胞生成素通过调节循环红细胞的数量来调节血液中的氧水平,并在成人的肾脏1-4或肝脏5,6以及胎儿或新生哺乳动物的肝脏7,8中产生。产生促红细胞生成素的精确细胞类型以及相同或不同细胞测量循环氧浓度并从而调节促红细胞生成素产生的机制(综述参见参考文献 9)均未知。已在成人骨髓 10、胎儿肝脏 11 或成人脾脏 12 中鉴定出对促红细胞生成素有反应的细胞。在红细胞生成祖细胞培养物中,促红细胞生成素刺激增殖和分化为更成熟的红细胞。然而,由于靶细胞群的杂质和异质性以及获得大量纯化激素的困难,详细的分子研究受到了阻碍。高度纯化的促红细胞生成素可用于治疗各种形式的贫血,特别是慢性肾功能衰竭13-15。在这里,我们描述了人促红细胞生成素基因的克隆以及促红细胞生成素cDNA克隆在瞬时哺乳动物表达系统中的表达,以产生具有生物活性的分泌产物。
The glycoprotein hormone erythropoietin regulates the level of oxygen in the blood by modulating the number of circulating erythrocytes, and is produced in the kidney1–4or liver5,6of adult and the liver7,8of fetal or neonatal mammals. Neither the precise cell types that produce erythropoietin nor the mechanisms by which the same or different cells measure the circulating oxygen concentration and consequently regulate erythropoietin production (for review see ref. 9) are known. Cells responsive to erythropoietin have been identified in the adult bone marrow10, fetal liver11or adult spleen12. In cultures of erythropoietic progenitors, erythropoietin stimulates proliferation and differentiation to more mature red blood cells. Detailed molecular studies have been hampered, however, by the impurity and heterogeneity of target cell populations and the difficulty of obtaining significant quantities of the purified hormone. Highly purified erythropoietin may be useful in the treatment of various forms of anaemia, particularly in chronic renal failure13–15. Here we describe the cloning of the human erythropoietin gene and the expression of an erythropoietin cDNA clone in a transient mammalian expression system to yield a secreted product with biological activity.