Transforming growth factor-ß-independent role of connective tissue growth factor in the development of liver fibrosis.
Am J Pathol
; 184(10): 2611-7, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-25108224
ABSTRACT
We previously identified transforming growth factor (TGF)-ß signaling as a fibronectin-independent mechanism of type I collagen fibrillogenesis following adult liver injury. To address the contribution of TGF-ß signaling during the development of liver fibrosis, we generated adult mice lacking TGF-ß type II receptor (TGF-ßIIR) from the liver. TGF-ßIIR knockout livers indeed showed a dominant effect in reducing fibrosis, but fibrosis still remained approximately 45% compared with control and fibronectin knockout livers. Unexpectedly, this was accompanied by significant up-regulation of connective tissue growth factor mRNA levels. Organized type I collagen networks in TGF-ßIIR knockout livers colocalized well with fibronectin. We provide evidence that elimination of TGF-ßIIR is not sufficient to completely prevent liver fibrosis. Our results indicate a TGF-ß-independent mechanism of type I collagen production and suggest connective tissue growth factor as its potent mediator. We advocate combined elimination of TGF-ß signaling and connective tissue growth factor as a potential therapeutic target by which to attenuate liver fibrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta
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Proteínas Serina-Treonina Quinases
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Receptores de Fatores de Crescimento Transformadores beta
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Fator de Crescimento do Tecido Conjuntivo
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Cirrose Hepática
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2014
Tipo de documento:
Article