Phosphatidylinositol 3-kinase is required for platelet-derived growth factor's actions on hepatic stellate cells

F. Marra, A. Gentilini, M. Pinzani, G. G. Choudhury, M. Parola, H. Herbst, M. U. Dianzani, G. Laffi, H. E. Abboud, P. Gentilini

Producción científica: Articlerevisión exhaustiva

187 Citas (Scopus)


Background and Aims: Platelet-derived growth factor (PDGF) is the most potent mitogen for hepatic stellate cells (HSCs) in vitro. The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI 3-K) activation in mediating the biological effects of PDGF on cultured HSCs and its involvement in vivo. Methods: HSCs were isolated from normal human livers. PI 3-K was assayed on phosphotyrosine or PDGF-receptor immunoprecipitates by in vitro kinase assay. Results: Incubation of HSCs with PDGF caused a time-dependent increase in PI 3-K activity. Immunoprecipitation of PDGF-α and -β receptors showed that both subunits associate with active PI 3-K in PDGF-stimulated HSCs. Wortmannin, a specific PI 3-K inhibitor, dose-dependently blocked PI 3-K activity induced by PDGF and inhibited DNA synthesis. PDGF (homodimer)-BB also stimulated HSC chemotaxis, which was inhibited by pretreatment with wortmannin. To explore the potential role of PI 3-K in vivo, liver homogenates from rats treated with CCl4 and from control rats were immunoprecipitated with anti-PDGF-β-receptor antibodies. Liver injury was associated with increased PDGF-β-receptor autophosphorylation, and greater PI 3-K activity associated with the receptor itself. Conclusions: This study shows that in cultured HSCs, PI 3-K activation is necessary for both mitogenesis and chemotaxis induced by PDGF and that this pathway is up-regulated during liver injury in vivo.

Idioma originalEnglish (US)
Páginas (desde-hasta)1297-1306
Número de páginas10
EstadoPublished - 1997
Publicado de forma externa

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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