Tissue-dependent expression of matrix proteins in human endothelin-1 transgenic mice.
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 interstitial 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.
Department of Nephrology, Charité, Humboldt-University of Berlin, 10117 Berlin, Germany.
Anja
A
Schwarz
Michael
M
Godes
Christa
C
Thöne-Reineke
Franz
F
Theuring
Christian
C
Bauer
Hans-Hellmut
HH
Neumayer
Berthold
B
Hocher
D000818:Animals; D024061:Collagen Type III / Q000032:analysis; D019332:Endothelin-1 / Q000032:analysis* / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000737:chemistry*; D007678:Kidney Glomerulus / Q000737:chemistry; D007797:Laminin / Q000032:analysis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000737:chemistry*
D024061:Collagen Type III; D019332:Endothelin-1; D016326:Extracellular Matrix Proteins; D007797:Laminin