Erythropoietin production by interstitial cells of hypoxic monkey kidneys

  title={Erythropoietin production by interstitial cells of hypoxic monkey kidneys},
  author={James W. Fisher and Stephen T. Koury and Thomas Ducey and Sandra Mendel},
  journal={British Journal of Haematology},
Previous studies which demonstrated that interstitial cells of the peritubular capillary bed of the kidneys are the site of erythropoietin (Epo) production have been performed in non‐primate species. In this study, kidneys from adult rhesus monkeys exposed to 18 h hypoxia (0.42 atm) with high serum (5685 mU/ml) and kidney (814 mU/g, includes serum EPO in the kidney) levels of Epo were compared with a kidney from a nonhypoxic normal rhesus monkey. Localization of Epo mRNA by in situ… 

Erythropoietin is produced by tubular cells of the rat kidney

Findings support some earlier findings that epo gene expression in response to cobalt salt stimulation of rat kidney occurs in transporting tubular epithelial cells.

Erythropoietin: Physiologic and Pharmacologic Aspects

  • J. Fisher
  • Medicine, Biology
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1997
It has been postulated that Epo decreases the rate which Epo-dependent progenitor cells undergo programed cell death (apoptosis), and there are two major signal transduction pathways activated by the Epo receptor: the JAK2-STAT5 pathway and the ras pathway.

Erythropoietin: Multiple Physiological Functions and Regulation of Biosynthesis

Novel functions ofEpo at these local sites and tissue-specific regulation of Epo production including a newly found potent regulator (estrogen) have been proposed, which rationalizes the specific functions of EpO produced by individual tissues.

Developmental regulation of erythropoietin and erythropoiesis.

Until recently, the major site of erythropoietin (Epo) production in the fetus was thought to be the liver, but studies have shown now that the Epo gene is expressed strongly in the fetal kidney, even in the temporary mesonephros.

Developmental regulation of erythropoietin and erythropoiesis.

Until recently, the major site of erythropoietin (Epo) production in the fetus was thought to be the liver, but studies have shown now that the Epo gene is expressed strongly in the fetal kidney, even in the temporary mesonephros.

A Review on Erythropietin in Pregnancy

Changes in circulatory system during pregnancy affect renal function, due to physiological increase in blood volume, and because erythropoietin is of renal origin, EPO concentration has been proved to increase 2-4-folds in the course of pregnancy and plateau is achieved after 20 weeks during the second trimester of pregnancy.

Erythropoietin: Physiology and Pharmacology Update 2

  • J. Fisher
  • Biology, Medicine
    Experimental biology and medicine
  • 2003
A novel erythropolesis-stimulating factor (NESP, darbepoetin) has been synthesized and when compared with rHu EPO, NESP has a higher carbohydrate content, a longer plasma half-life, the amino acid sequence differs from that of native human EPO at five positions, and has been reported to maintain hemoglobin levels just as effectively in patients with chronic renal failure as rHuEPO at less frequent dosing.

High glucose stimulates the expression of erythropoietin in rat glomerular epithelial cells

It is concluded that high glucose stimulates erythropoietin production and erythrooietsin receptor phosphorylation in rat glomerular epithelial cells.

Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

Data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production.



Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney.

It is demonstrated that peritubular cells, most likely endothelial cells, constitute the major site of Epo production in the murine hypoxic kidney.

Erythropoietin gene expression in fetal and adult sheep kidney.

The findings confirm that the kidney is an important site of Epo production, in the sheep, from at least 0–4 gestation, but also show that there is no ontogenic change in the cellular site of production within the kidney.

Co-localization of erythropoietin mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin.

Non-radioactive in situ hybridization with a digoxigenin-labeled cRNA probe is used to localize cells that produce erythropoietin (EPO) in kidneys of anemic rats and indicates that peritubular fibroblasts are cellular sites for production of ery Anthropogenic hormone.

Localization of cells producing erythropoietin in murine liver by in situ hybridization.

It is demonstrated that hepatocytes are responsible for production of EPO in both transgenic and nontransgenic mice and that a second cell type that is similar in morphology to EPO-producing interstitial cells in the kidney also producesEPO in the livers of nontransogenic mice.

Cellular sites of extrarenal and renal erythropoietin production in anaemic rats

It is suggested that hepatocytes are the major source of extrarenal erythropoietin with nonparenchymal liver cells contributing less than 1% to total hepatic erythroietin production.

Quantitation of erythropoietin-producing cells in kidneys of mice by in situ hybridization: correlation with hematocrit, renal erythropoietin mRNA, and serum erythropoietin concentration.

The results suggest that following an acute blood loss and during the recovery from a blood loss, the capacity to deliver oxygen, as represented by hematocrit, is the major regulator of EP production.

Identification of the renal erythropoietin-producing cells using transgenic mice.

In transgenic mice bearing Epo-TAg at homologous and heterologous insertion sites, renal expression was restricted to a population of cells in the interstitium of the cortex and outer medulla, and characterization shows that these are the fibroblast-like type I interstitial cells.

Recent advances in erythropoietin research.

  • J. Fisher
  • Biology, Medicine
    Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques
  • 1993
A humoral regulation of erythropoiesis was proposed by Carnot and Deflandre in 1906 but this proposal was not substantiated until the work of Hjort in 1936 and Erslev in 1953 in which these investigators found that large volumes of plasma from rabbits following bleeding produced a marked reticulocytosis when injected into recipient animals.

Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization.

In situ hybridization was used to localize the cells that produce erythropoietin (EP) in anemic murine kidneys and an uncommon, but specific type of cell was intensely labeled in the cortices of anemic kidneys.

Isolation and characterization of genomic and cDNA clones of human erythropoietin

The cloning of the human erythropoietin gene and the expression of an erythrocytes cDNA clone in a transient mammalian expression system to yield a secreted product with biological activity are described.