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Titolo:
CHARACTERIZATION OF THE RENAL PHENOTYPE OF TRANSGENIC RATS EXPRESSINGTHE HUMAN ENDOTHELIN-2 GENE
Autore:
HOCHER B; LIEFELDT L; THONEREINEKE C; ORZECHOWSKI HD; DISTLER A; BAUER C; PAUL M;
Indirizzi:
FREE UNIV BERLIN,KLINIKUM BENJAMIN FRANKLIN,INST KLIN PHARMAKOL,HINDENBURGDAMM 30 D-12200 BERLIN GERMANY FREE UNIV BERLIN,KLINIKUM BENJAMIN FRANKLIN,INST KLIN PHARMAKOL D-12200 BERLIN GERMANY FREE UNIV BERLIN,INST MOL BIOL & BIOCHEM D-12200 BERLIN GERMANY FREE UNIV BERLIN,KLINIKUM CHARITE,DEPT NEPHROL D-12200 BERLIN GERMANY
Titolo Testata:
Hypertension
fascicolo: 2, volume: 28, anno: 1996,
pagine: 196 - 201
SICI:
0194-911X(1996)28:2<196:COTRPO>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
DISEASE PROGRESSION; RECEPTOR; INJURY; CLONING; SYSTEM; VEIN;
Keywords:
HUMAN; ENDOTHELINS; RATS, TRANSGENIC; KIDNEY; GLOMERULAR SCLEROSIS; BLOOD PRESSURE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
28
Recensione:
Indirizzi per estratti:
Citazione:
B. Hocher et al., "CHARACTERIZATION OF THE RENAL PHENOTYPE OF TRANSGENIC RATS EXPRESSINGTHE HUMAN ENDOTHELIN-2 GENE", Hypertension, 28(2), 1996, pp. 196-201

Abstract

We have previously established a transgenic rat model termed TGR(hET-2)37 overexpressing the human endothelin-2 (ET-2) gene with high renaltransgene expression. This renal overexpression is of pathophysiological interest because a long-term activated paracrine renal endothelin system has been implicated in chronic renal failure due to progressiveglomerular injury. Therefore, our aim in the present study was to analyze renal transgene expression in detail and address the question of whether transgene expression causes phenotypic and functional changes in the kidney. We used reverse transcription-polymerase chain reactionand in situ hybridization techniques for transgene expression analysis. Tissue ET-2 concentrations were measured with a specific radioimmunoassay. For histological evaluation of renal tissue, all samples were subjected to hematoxylin-eosin and periodic acid-Schiff staining. Renal tissue ET-2 concentrations were significantly increased in TGR(hET-2)37 rats. Using in situ hybridization, we found that the human ET-2 gene was almost exclusively expressed within the glomeruli. The glomerular transgene expression resulted in a significantly increased glomerular injury score and likewise in a significantly increased protein excretion, whereas glomerular filtration rate was not altered. Blood pressure was similar in TGR(hET-2)37 rats and age-matched controls, suggesting that the local changes in the kidney were correlated with paracrine endothelin actions. In conclusion, our study revealed that the majorrenal expression site of the human ET-2 transgene in TGR(hET-2)37 rats was within the glomeruli and caused the development of glomerulosclerosis with significantly increased protein excretion that is independent of blood pressure. We suggest that TGR(hET-2)37 rats are a new monogenetic animal model for study of the paracrine renal endothelin system and its involvement in renal pathophysiology.

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Documento generato il 01/12/20 alle ore 09:54:31