The hepatocyte is a direct target for transforming-growth factor beta activation via the insulin-like growth factor II/mannose 6-phosphate receptor.
J Hepatol
; 38(2): 156-63, 2003 Feb.
Article
en En
| MEDLINE
| ID: mdl-12547403
ABSTRACT
BACKGROUND/AIMS:
The cation-independent mannose 6-phosphate receptor (CIMPR) is overexpressed in hepatocytes during liver regeneration and has been implicated in the maturation of latent pro-transforming growth factor beta (TGFbeta). In this study, we have (1) kinetically characterized the changes in CIMPR expression in regenerating liver and cultured proliferating hepatocytes; and (2) assessed the contribution of hepatocyte via the CIMPR to latent pro-TGFbeta activation.METHODS:
The expression of CIMPR protein and mRNA in livers collected after partial hepatectomy and hepatocyte primary cultures was analyzed by Western and Northern blotting. Activity of latent pro-TGFbeta was assessed by inhibition of [3H] methylthymidine incorporation into DNA.RESULTS:
The expression of the CIMPR protein and/or mRNA progressively increased after 8 h in regenerating liver and 42-46 h in cultured hepatocytes, prior to the onset of DNA replication. Both mature TGFbeta and latent pro-TGFbeta inhibited epidermal growth factor-stimulated DNA synthesis in hepatocytes in a dose-dependent manner. The effect of latent pro-TGFbeta was reversed by two ligands of the CIMPR beta-galactosidase, a mannose 6-phosphate containing protein, and a CIMPR antibody.CONCLUSIONS:
(1) The induction of the CIMPR gene during liver regeneration and hepatocyte culture occurs in mid G1 phase; and (2) the CIMPR mediates latent proTGFbeta activation and thus may act, by targeting TGFbeta to hepatocytes, as a negative regulator of hepatocyte growth.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Receptor IGF Tipo 2
/
Hepatocitos
Límite:
Animals
Idioma:
En
Revista:
J Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Francia