Physiologic Regulation and Tissue Localization of Renal Erythropoietin Messenger RNA

Although erythropoietin (Epo) is produced primarily by the kidneys in response to hypoxia, the precise cell type(s) and mechanisms by which these cells regulate production are poorly understood. In the experiments we report, the kinetics of renal Epo production in response to acute hypoxia and the i...

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Bibliographic Details
Published in:Blood 1987-07, Vol.70 (1), p.316-318
Main Authors: Schuster, Stephen J., Wilson, Jean H., Erslev, Allan J., Jaime, Caro
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Collodion
Electrophoresis, Polyacrylamide Gel
Erythropoietin - biosynthesis
Erythropoietin - genetics
Fundamental and applied biological sciences. Psychology
Hypoxia - physiopathology
Kidney - analysis
Kidney - cytology
Kidney - physiology
Kidney Glomerulus - cytology
Kidney Glomerulus - metabolism
Kidney Tubules - metabolism
Kinetics
Male
Rats
Rats, Inbred Strains
RNA, Messenger - analysis
RNA, Messenger - metabolism
Time Factors
Tissue Distribution
Tissue Extracts
Vertebrates: blood, hematopoietic organs, reticuloendothelial system
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Summary:Although erythropoietin (Epo) is produced primarily by the kidneys in response to hypoxia, the precise cell type(s) and mechanisms by which these cells regulate production are poorly understood. In the experiments we report, the kinetics of renal Epo production in response to acute hypoxia and the intrarenal localization of cellular Epo synthesis were studied at the level of Epo mRNA. Erythropoietin mRNA expression was determined by Northern blot analysis of rat kidney RNAs using a probe derived from the mouse Epo gene. Renal Epo mRNA content increased as early as 1 hour after initiation of hypoxia and continued to accumulate during 4 hours of stimulation. Discontinuation of the hypoxic stimulus resulted in rapid decay of mRNA levels. Kidney and plasma Epo levels measured by radioimmunoassay paralleled, with respective lag times, the changes in renal Epo mRNA content, suggesting that Epo production in response to acute hypoxia represents de novo synthesis and is regulated by changes in Epo mRNA. Northern blot analysis of RNAs extracted from separated glomerular and tubular tissue fractions revealed Epo mRNA in the tubular fraction, whereas glomerular tissue did not contain Epo mRNA. Thus, the site of cellular Epo synthesis is located in the renal tubule or its interstitium and not in the glomerular tuft.© 1987 by Grune & Stratton, Inc. 0006-4971/87/7001-0050$3.00/0
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V70.1.316.316