Endothelin-1 (ET-1) is a potent pro-fibrotic growth factor. However, little is known about its specific effects on the synthesis of matrix proteins in vivo. We used male 12-month-old ET-1 transgenic mice characterized by transgene expression in the kidney and (to a lesser extent) in the heart. Global cardiac and renal matrix protein synthesis was analysed after Sirius Red and periodate–Schiff staining. Specific expression of collagen types I, III and IV, laminin and fibronectin was examined using immunohistochemistry followed by computer-aided image analysis. Analysis of blood pressure revealed that mean arterial blood pressure was similar in ET-1 transgenic mice and controls. The total cardiac matrix protein content was increased in the myocardium of ET-1 transgenic mice. Analysis of specific cardiac matrix proteins showed increased cardiac expression of collagen type III (+211%; P<0.001) and laminin (+128%; P<0.01) in transgenic mice. The expression of collagen types I and IV and fibronectin was not altered. Global analysis of renal matrix proteins confirmed earlier studies showing pronounced interstitital fibrosis and glomerulosclerosis. Laminin expression was markedly increased in the glomerula (+152%; P<0.01) and even more so in the interstitium (+211%; P<0.001), whereas expression of collagen type III was reduced in glomerula (-48%; P<0.01) and interstitial tissue (-55%; P<0.01) of ET-1 transgenic mice. In conclusion, a primary overexpression of ET-1 does not cause uniformly enhanced synthesis of matrix proteins. In contrast, the effects of ET-1 on the matrix protein pattern is tissue-specific. The major renal and cardiac alterations in matrix proteins induced by ET-1 is a marked enhancement of laminin expression.
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September 2002
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Conference Article|
September 01 2002
Tissue-dependent expression of matrix proteins in human endothelin-1 transgenic mice
Anja SCHWARZ;
Anja SCHWARZ
*Department of Nephrology, Charité, Humboldt-University of Berlin, 10117 Berlin, Germany
†Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany
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Michael GODES;
Michael GODES
*Department of Nephrology, Charité, Humboldt-University of Berlin, 10117 Berlin, Germany
†Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany
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Christa THÖNE-REINEKE;
Christa THÖNE-REINEKE
†Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany
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Franz THEURING;
Franz THEURING
‡Department of Pharmacology and Toxicology, Charité, Humboldt-University of Berlin, 10117 Berlin, Germany
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Christian BAUER;
Christian BAUER
†Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany
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Hans-Hellmut NEUMAYER;
Hans-Hellmut NEUMAYER
*Department of Nephrology, Charité, Humboldt-University of Berlin, 10117 Berlin, Germany
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Berthold HOCHER
*Department of Nephrology, Charité, Humboldt-University of Berlin, 10117 Berlin, Germany
†Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany
Dr Berthold Hocher, Universitätsklinikum Charité, Klinik für Nephrologie, 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): 39S–43S.
Citation
Anja SCHWARZ, Michael GODES, Christa THÖNE-REINEKE, Franz THEURING, Christian BAUER, Hans-Hellmut NEUMAYER, Berthold HOCHER; Tissue-dependent expression of matrix proteins in human endothelin-1 transgenic mice. Clin Sci (Lond) 1 September 2002; 103 (s2002): 39S–43S. doi: https://doi.org/10.1042/CS103S039S
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