Isolation and characterization of genomic and cDNA clones of human erythropoietin

Abstract

The glycoprotein hormone erythropoietin regulates the level of oxygen in the blood by modulating the number of circulating erythrocytes, and is produced in the kidney or liver of adult and the liver of 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 are known. Cells responsive to erythropoietin have been identified in the adult bone marrow, fetal liver or adult spleen. 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 failure. 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.

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure

“…Erythropoietin is required for proliferation and terminal differentiation of erythroid progenitors and precursors and is a major determinant of red cell mass (1,2,3). The kidney is the most important site for the release of renin, an enzyme that cleaves angiotensinogen to angiotensin I (4).…”

Localization of renal erythropoietin and the role of Ia antigen expression in hypoxic rat glomeruli.

“…erythropoietin (EPO) ; Ia antigen ; hypoxia Erythropoietin (EPO) is the glycoprotein hormone which is the primary factor regulating erythropoiesis, and is produced by the kidney. Although the molecular structure of EPO has been described earlier (Jacobs et al 1985 ;Lin et al 1985), the producing cells or sites have remained unclear. There are many reports about the localization of EPO production within the kidney.…”

The Effects of Intrarenal Infusion of Recombinant Human Erythropoietin on Mean Arterial Pressure and Renal Hemodynamics in Anesthetized Rabbits.

“…Using this preparation, the present study has clearly demonstrated that rHuEPO has no direct effects on MAP or renal hemodynamics in anesthetized rabbits without renal failure. Since molecular cloning and expression of a biological active form into mammalian cells (Jacobs et al 1985 ;Lin et al 1985), rHuEPO has been used clinically for treatment of anemia associated with chronic renal failure (Winearls et al 1986;Eschbach et al 1987;Mayer et al 1988). rHuEPO has been shown to be effective in reversing anemia in hemodialysis patients.…”