Overexpression of endothelin-1 in bile duct ligated rats: correlation with activation of hepatic stellate cells and portal pressure.
J Hepatol
; 34(1): 38-45, 2001 Jan.
Article
en En
| MEDLINE
| ID: mdl-11211905
BACKGROUND/AIMS: Hepatic stellate cells (HSC) are involved in the pathogenesis of liver fibrosis; although ET-1 is increased in cirrhosis, its pathophysiological role in fibrogenesis and portal hypertension remains controversial. The aim of this study was to investigate splanchnic hemodynamics and to correlate them with changes in ET-1 expression and HSC activation in bile duct ligated (BDL) rats. METHODS/RESULTS: Expression of the ET-1 gene was increased early as measured by quantitative reverse transcriptase-polymerase chain reaction (6-fold 3 days after BDL) whereas ET-1 peptide measured by RIA increased significantly only in the late phase (30-fold at 28 days). There was a linear correlation between portal pressure and the amount of ET-1 in the portal vein (r = 0.66; P = 0.003), as well as between ET-1 and the volume fraction of myofibroblasts (r = 0.80, P < 10(-7)) as assessed by morphometry and immunohistochemical staining using alpha-smooth muscle actin. CONCLUSIONS: During chronic liver injury activation of HSCs and of preproET-1 mRNA is accentuated in the early phase after BDL. The late increase in ET-1 peptide may indicate that this peptide is only secondarily involved in HSC activation. The correlation between ET-1 in portal vein and portal pressure suggests that ET-1 may play an important role in the development of portal hypertension.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colestasis
/
Endotelina-1
/
Hipertensión Portal
/
Hígado
/
Cirrosis Hepática Experimental
Límite:
Animals
Idioma:
En
Revista:
J Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Países Bajos