Transforming growth factor beta1 helps maintain differentiated functions in mitogen-treated primary rat hepatocyte cultures.
Mol Cell Biol Res Commun
; 1(3): 188-95, 1999 Jun.
Article
en En
| MEDLINE
| ID: mdl-10425225
Mechanisms that control function and repair of the injured liver remain unclear. We hypothesized that after liver injury, elevated blood TGF-beta1 levels may reflect an adaptive response to help maintain differentiated functions in surviving hepatocytes affected by excessive amounts of HGF. We thus studied the effect of HGF, EGF, TGF-beta1, HGF + TGF-beta1, or EGF + TGF-beta1 on the expression of liver-enriched transcription factors and genes which remain under their regulatory activity. The peak [3H]thymidine uptake induced by 20 ng/ml of either HGF or EGF was seen after 72 h; however, DNA binding of C/EBP and HNF1 decreased already after 6 h (electrophoretic mobility shift assay). Addition of TGF-beta1 antagonized these effects. Also at the mRNA level, TGF-beta1 counteracted at one point or another the decrease in C/EBPalpha, C/EBPbeta, HNF1beta, and HNF4 expression; HNF1alpha and COUP-TF showed similar responses and, additionally, were downregulated by TGF-beta1 at 24 h (Northern blot). Albumin and apolipoprotein B mRNA levels were decreased after 24-h treatment with HGF, whereas addition of TGF-beta1 increased their levels. The same pattern was found with EGF, but not until 48 h. PEPCK mRNA was dramatically lowered with either EGF or HGF, and TGF-beta1 did not counteract these effects. Id-1 was expressed only in cultures treated for 24 and 48 h with both the mitogen (EGF, HGF) and TGF-beta1 and in those treated for 48 h with TGF-beta1 alone.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Hígado
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Biol Res Commun
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos