Raf and mitogen-activated protein kinase regulate stellate cell collagen gene expression.
J Biol Chem
; 271(19): 11039-42, 1996 May 10.
Article
em En
| MEDLINE
| ID: mdl-8626642
ABSTRACT
Hepatic stellate cells become activated into myofibroblast-like cells during the early stages of hepatic injury associated with fibrogenesis. The subsequent dysregulation of hepatic stellate cell collagen gene expression is a central pathogenetic step during the development of cirrhosis. The cytoplasmic Raf and mitogen-activated protein (MAPK) kinases were found to differentially regulate alpha I(I) collagen gene expression in activated stellate cells. This suggests an unappreciated branch point exists between Raf and MAPK. A MAPK-stimulatory signal was mapped to the most proximal NF-1 and Sp-1 binding domains of the 5'-untranslated region of the collagen gene. A Raf-inhibitory signal was mapped to a further upstream binding domain involving a novel 60-kDa DNA-binding protein (p60). The cell-specific expression and induction of p60 in stellate cells during the early stages of hepatic fibrogenesis in vivo suggest a central role for this pathway during liver injury and stellate cell activation.
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Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Colágeno
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
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Fígado
Limite:
Animals
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article