Adenoviral dominant-negative soluble PDGFRß improves hepatic collagen, systemic hemodynamics, and portal pressure in fibrotic rats.
J Hepatol
; 57(5): 967-73, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-22820479
ABSTRACT
BACKGROUND & AIMS:
Platelet-derived growth factor (PDGF) is the most potent stimulus for proliferation and migration of stellate cells. PDGF receptor ß (PDGFRß) expression is an important phenotypic change in myofibroblastic cells that mediates proliferation and chemotaxis. Here we analyzed the relationship between PDGFRß expression, hemodynamic deterioration, and fibrosis in CCl(4)-treated rats. Thereafter, we investigated the effects produced by an adenovirus encoding a dominant-negative soluble PDGFRß (sPDGFRß) on hemodynamic parameters, PDGFRß signaling pathway, and fibrosis.METHODS:
Mean arterial pressure, portal pressure, PDGFRß mRNA expression, and hepatic collagen were assessed in 6 controls and 21 rats induced to hepatic fibrosis/cirrhosis. Next, 30 fibrotic rats were randomized into three groups receiving iv saline and an adenovirus encoding for sPDGFRß or ß-galactosidase. After 7days, mean arterial pressure, portal pressure, serum sPDGFRß, and hepatic collagen were measured.RESULTS:
CCl(4)-treated animals for 18weeks showed a significantly higher increase in PDGFRß mRNA compared to those treated for 13weeks and control rats. In CCl(4)-treated rats, the fibrous tissue area ranged from moderate to severe fibrosis. A direct relationship between the degree of fibrosis, hemodynamic changes, and PDGFRß expression was observed. Fibrotic rats transduced with the adenovirus encoding sPDGFRß showed increased mean arterial pressure, decreased portal pressure, lower activation of the PDGFRß signaling pathway, and reduced hepatic collagen than fibrotic rats receiving ß-galactosidase or saline.CONCLUSIONS:
PDGFRß activation closely correlates with hemodynamic disorders and increased fibrosis in CCl(4)-treated rats. Adenoviral dominant negative soluble PDGFRß improved fibrosis. As a result, the hemodynamic abnormalities were ameliorated.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenoviridae
/
Colágeno
/
Pressão na Veia Porta
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Receptor beta de Fator de Crescimento Derivado de Plaquetas
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Hemodinâmica
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Fígado
/
Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha