Transgenic overexpression of erythropoietin (Epo) in mice increases haematocrit to a mean of 80% in adult mice, leading to an increase in blood viscosity and volume. As a consequence, renal tissue endothelin-1 (ET-1) concentrations are significantly elevated in erythropoietin-overexpressing (Epo+) mice (mean±S.E.M; Epo+, 798±71; Epo-, 400±25pg/g tissue; P<0.01). To investigate the pattern of expression of the primary translation product of the ET-1 gene, prepro-ET-1, in kidneys of (Epo+) mice, we generated crossbred mice overexpressing the human EPO gene with mice carrying a reporter gene construct expressing the LacZ gene under the control of the human prepro-ET-1 promotor sequence (LacZ+/Epo+). For comparison, we generated (LacZ+/Epo-) mice from the same strains. After Bluo-Gal staining of frozen kidney sections (n = 10 in each group), intracellular blue precipitates as indicators of prepro-ET-1 promotor activity were detectable in tubular and vascular endothelium and glomerular cells in (LacZ+/Epo-) as well as (LacZ+/Epo+) mice. Comparison of the amount of blue precipitates by semiquantitative scoring showed a significant increase in reporter gene activity in tubular epithelium of (LacZ+/Epo+) mice (mean±S.E.M.; LacZ+/Epo+, 1.64±0.18; LacZ+/Epo-, 1.00±0.19; P<0.05). Reporter gene activity was not significantly elevated in epithelium of small intrarenal arteries of (LacZ+/Epo+) mice (mean±S.E.M.; LacZ+/Epo+, 0.86±0.14; LacZ+/Epo-, 0.38±0.21; P = 0.08) and was similar in glomerular cells (mean±S.E.M.; LacZ+/Epo+, 1.28±0.16; LacZ+/Epo-, 1.14±0.21; P = 0.6). The main source of elevated ET-1 tissue concentration in kidneys of (Epo+) mice therefore seems more likely to be tubular than vascular endothelium or glomerular cells.
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September 2002
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September 01 2002
Pattern of prepro-endothelin-1 expression revealed by reporter-gene activity in kidneys of erythropoietin-overexpressing mice
Torsten SLOWINSKI;
Torsten SLOWINSKI
*Department of Nephrology, University Hospital Charité, Humboldt University of Berlin, D-10117 Berlin, Germany
†Institute of Molecular Biology and Biochemstry, Free University of Berlin, D-14195 Berlin, Germany
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Norma SCHULZ;
Norma SCHULZ
*Department of Nephrology, University Hospital Charité, Humboldt University of Berlin, D-10117 Berlin, Germany
†Institute of Molecular Biology and Biochemstry, Free University of Berlin, D-14195 Berlin, Germany
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Frank T. RUSCHITZKA;
Frank T. RUSCHITZKA
‡Institute of Physiology, Institutes of Physiology and Veterinary Physiology, University of Zürich, CH-8057 Zürich, Switzerland
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Thomas QUASCHNING;
Thomas QUASCHNING
‡Institute of Physiology, Institutes of Physiology and Veterinary Physiology, University of Zürich, CH-8057 Zürich, Switzerland
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Christian BAUER;
Christian BAUER
†Institute of Molecular Biology and Biochemstry, Free University of Berlin, D-14195 Berlin, Germany
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Franz THEURING;
Franz THEURING
§Institute of Pharmacology and Toxicology, University Hospital Charité, Humboldt University of Berlin, D-10117 Berlin, Germany
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Hans-H. NEUMAYER;
Hans-H. NEUMAYER
*Department of Nephrology, University Hospital Charité, Humboldt University of Berlin, D-10117 Berlin, Germany
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Max GASSMANN;
Max GASSMANN
‡Institute of Physiology, Institutes of Physiology and Veterinary Physiology, University of Zürich, CH-8057 Zürich, Switzerland
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Berthold HOCHER
*Department of Nephrology, University Hospital Charité, Humboldt University of Berlin, D-10117 Berlin, Germany
†Institute of Molecular Biology and Biochemstry, Free University of Berlin, D-14195 Berlin, Germany
Dr B. Hocher, Department of Nephrology, University Hospital Charité, Humboldt University of Berlin, Schumannstrasse 20-21, 10098 Berlin, Germany (e-mail [email protected]).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 44S–47S.
Citation
Torsten SLOWINSKI, Norma SCHULZ, Frank T. RUSCHITZKA, Thomas QUASCHNING, Christian BAUER, Franz THEURING, Hans-H. NEUMAYER, Max GASSMANN, Berthold HOCHER; Pattern of prepro-endothelin-1 expression revealed by reporter-gene activity in kidneys of erythropoietin-overexpressing mice. Clin Sci (Lond) 1 September 2002; 103 (s2002): 44S–47S. doi: https://doi.org/10.1042/CS103S044S
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