Erythropoiesis in Anephric Man *

Nathan, David G.; Schupak, Eugene; Stohlman, Frederick; Merrill, John P.

doi:10.1172/jci105089

Cited by 114 publications

(28 citation statements)

References 22 publications

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“…Moreover, nonrenal tissues, most likely including the liver, can contribute to erythropoietin production in anephric, hypoxemic adults. [9][10][11] We showed recently that erythropoietin production was markedly induced in adult hepatocytes lacking all 3 EglN family members, supporting the idea that the liver can contribute to circulating erythropoietin levels in the setting of chronic kidney disease. 12 Orally available EglN inhibitors have been shown to stimulate RBC production in preclinical models and are currently being tested in the clinical setting as a potential treatment for anemia, including anemia linked to chronic kidney disease.…”

Section: Introductionmentioning

confidence: 65%

Treatment of erythropoietin deficiency in mice with systemically administered siRNA

Querbes

Bogorad

Moslehi

et al. 2012

Blood

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Anemia linked to a relative deficiency of renal erythropoietin production is a significant cause of morbidity and medical expenditures in the developed world. Recombinant erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover, some patients become refractory to erythropoietin because of increased production of factors such as hepcidin. During fetal life, the liver, rather than the kidney, is the major source of erythropoietin. In the present study, we show that it is feasible to reactivate hepatic erythropoietin production and suppress hepcidin levels using systemically delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the liver, leading to improved RBC production in models of anemia caused by either renal insufficiency or chronic inflammation with enhanced hepcidin production. (Blood. 2012;120(9): [1916][1917][1918][1919][1920][1921][1922]

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Section: Introductionmentioning

confidence: 65%

Treatment of erythropoietin deficiency in mice with systemically administered siRNA

Querbes

Bogorad

Moslehi

et al. 2012

Blood

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“…Organ ablation studies in rats (Jacobson et al 1957) and man (Nathan et al 1964) firmly established that the kidney was the major site but not the sole site of Epo production. These findings led Eugene Goldwasser and his colleagues to undertake an intense and prolonged effort to isolate Epo.…”

mentioning

confidence: 99%

Erythropoietin

Bunn

2013

Cold Spring Harbor Perspectives in Medicine

208

171

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During the past century, few proteins have matched erythropoietin (Epo) in capturing the imagination of physiologists, molecular biologists, and, more recently, physicians and patients. Its appeal rests on its commanding role as the premier erythroid cytokine, the elegant mechanism underlying the regulation of its gene, and its remarkable impact as a therapeutic agent, arguably the most successful drug spawned by the revolution in recombinant DNA technology. This concise review will begin with a synopsis of the colorful history of this protein, culminating in its purification and molecular cloning. It then covers in more detail the contemporary understanding of Epo's physiology as well as its structure and interaction with its receptor. A major part of this article focuses on the regulation of the Epo gene and the discovery of HIF, a transcription factor that plays a cardinal role in molecular adaptation to hypoxia. In the concluding section, a synopsis of Epo's role in disorders of red blood cell production will be followed by an assessment of the remarkable impact of Epo therapy in the treatment of anemias, as well as concerns that provide a strong impetus for the development of even safer and more effective treatment.

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“…Evaluation of RBC survival of patients treated with maintenance hemodialysis using 51Cr and Di (isopropofluro) 32p techniques revealed that the half-life of the RBC is markedly reduced (5) and that increasing the frequency of dialysis did not normalize the halflife of the cells (6). These observations indicate that the serum factor (or factors) responsible for the reduced survival of the RBC was not effectively removed by dialysis.…”

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confidence: 99%

Effect of Parathyroid Hormone on Osmotic Fragility of Human Erythrocytes

Bogin¹,

Massry²,

Levi³

et al. 1982

J. Clin. Invest.

185

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A B S T R A C T The survival of erythrocytes (RBC) is shortened in uremia, and it has been shown that calcium influx into RBC evoked crenation and increased their rigidity. The high blood levels of parathyroid hormone (PTH) may augment entry of calcium into RBC and hence affect their integrity. We examined the effect of PTH on osmotic fragility of human RBC and investigated the mechanisms through which PTH interacts with RBC. Both the amino-terminal (1-34) PTH and the intact (1-84) PTH, but not the carboxy-terminal (53-84) PTH, produced significant increases in osmotic fragility. This effect was abolished by prior inactivation of the hormone. There was a dose-response relationship between both moieties of PTH and the increase in osmotic fragility. This action of PTH required calcium, was mimicked by calcium ionophore, and was partially blocked by verapamil. PTH caused significant influx of 45Ca into RBC, which was not associated with potassium leak. The hormone did not affect water content of RBC. Scanning electron microscopy revealed that the incubation of RBC with PTH was associated with the appearance of membrane filamentous extensions, which anchor RBC together.Inhibition of glycolytic activity of RBC with NaF or inhibition of Na-K-activated ATPase with ouabain did not abolish the effect of PTH on osmotic fragility. PTH did not stimulate RBC Na-K-activated ATPase or Mg-dependent ATPase but caused marked and significant stimulation of Ca-activated ATPase. The basal activity of the RBC adenylate cyclase was low and PTH produced only a modest stimulation of this enzyme. Both cyclic AMP and dibutyryl cyclic AMP had no effect on osmotic fragility.The data indicate that: (a) the RBC is a target organ for PTH, (b) the hormone increases osmotic fragility

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Erythropoiesis in Anephric Man *

Cited by 114 publications

References 22 publications

Treatment of erythropoietin deficiency in mice with systemically administered siRNA

Treatment of erythropoietin deficiency in mice with systemically administered siRNA

Erythropoietin

Effect of Parathyroid Hormone on Osmotic Fragility of Human Erythrocytes

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