Erythropoietin production by interstitial cells of hypoxic monkey kidneys

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 hybridization was carried out with either anti‐sense or sense RNA probes generated from a 645 base pair KpnI–BglII fragment of a monkey Epo cDNA. Epo mRNA was demonstrated only in interstitial cells in the peritubular capillary bed of the hypoxic and normal monkey kidneys utilizing the antisense probe. The finding that the same type of cell that produces EPO in mice, rats and sheep also produces EPO in a higher primate species strongly supports the contention that renal interstitial cells also produce EPO in the human.

[1]  E. Wintour,et al.  Erythropoietin gene expression in fetal and adult sheep kidney , 1995, British journal of haematology.

[2]  H. Lin,et al.  Transgenic mice carrying the erythropoietin gene promoter linked to lacZ express the reporter in proximal convoluted tubule cells after hypoxia. , 1994, Blood.

[3]  P. Ratcliffe,et al.  Expression of a homologously recombined erythopoietin-SV40 T antigen fusion gene in mouse liver: evidence for erythropoietin production by Ito cells. , 1994, Blood.

[4]  P. Ratcliffe,et al.  Identification of the renal erythropoietin-producing cells using transgenic mice. , 1993, Kidney international.

[5]  E. Wintour,et al.  The sheep erythropoietin gene: molecular cloning and effect of hemorrhage on plasma erythropoietin and renal/liver messenger RNA in adult sheep , 1993, Molecular and Cellular Endocrinology.

[6]  M. Le Hir,et al.  Co-localization of erythropoietin mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[7]  S. Koury,et al.  Cellular sites of extrarenal and renal erythropoietin production in anaemic rats , 1992, British journal of haematology.

[8]  R. W. Jones,et al.  Functional analysis of an oxygen-regulated transcriptional enhancer lying 3' to the mouse erythropoietin gene. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. Weinmann,et al.  Enhancer element at the 3'-flanking region controls transcriptional response to hypoxia in the human erythropoietin gene. , 1991, The Journal of biological chemistry.

[10]  S. Antonarakis,et al.  Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  G. Semenza,et al.  Localization of cells producing erythropoietin in murine liver by in situ hybridization. , 1991, Blood.

[12]  A. Maxwell,et al.  Erythropoietin production in kidney tubular cells , 1990, British journal of haematology.

[13]  D. Simon,et al.  The murine erythropoietin gene is localized on chromosome 5. , 1988, Blood.

[14]  F. Wendling,et al.  Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney. , 1988, The Journal of clinical investigation.

[15]  M. Koury,et al.  Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. , 1988, Blood.

[16]  E. Goldwasser,et al.  Cloning, sequencing, and evolutionary analysis of the mouse erythropoietin gene , 1986, Molecular and cellular biology.

[17]  C. Shoemaker,et al.  Murine erythropoietin gene: cloning, expression, and human gene homology , 1986, Molecular and cellular biology.

[18]  C. H. Lin,et al.  Cloning and expression of the human erythropoietin gene. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Fisher,et al.  Increased levels of erythropoietin in kidney extracts of rats treated with cobalt and hypoxia. , 1983, The American journal of physiology.

[20]  J. Fisher.  Recent advances in erythropoietin research. , 1993, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[21]  I. Rich.  The site of erythropoietin production: localization of erythropoietin mRNA by radioactive in situ hybridization. , 1991, Blood.

[22]  M. Koury,et al.  Quantitation of erythropoietin-producing cells in kidneys of mice by in situ hybridization: correlation with hematocrit, renal erythropoietin mRNA, and serum erythropoietin concentration. , 1989, Blood.

[23]  E. Fritsch,et al.  Isolation and characterization of genomic and cDNA clones of human erythropoietin , 1985, Nature.