Z Gastroenterol 2004; 42 - AB_2_73
DOI: 10.1055/s-2004-816098

Specific expression of the homeobox transcription factor Prox1 in hepatocytes in vitro, and during liver damage and regeneration in vivo

J Dudas 1, M Papoutsi 2, M Stefan 2, D Batusic 1, A Elmaouhoub 1, V Cimica 1, T Pieler 3, G Ramadori 1, J Wilting 2
  • 1Abt. Gastroenterologie und Endokrinologie, Uniklinikum Göttingen
  • 2Abt. Pediatrie, Uniklinikum Göttingen
  • 3Institut für Biochemie, Universität Göttingen

Aims: Prox1 is one of the earliest markers of the hepatic bud. A 70% reduction of the number of hepatoblasts has been observed in Prox1-/- mice. Prox1 may regulate proliferation, migration and cell-matrix interactions during liver development.

Methods: Prox1 expression was determined at RNA and protein levels in whole livers, in cells isolated from rat livers, in met-murine hepatocytes (MMH), and in human hepatoma cells. For mRNA expression, northern blot and real time PCR, for protein expression western blot and immunostaining were used. Animal models: liver damage induced by CCl4 treatment in Wistar rats, partial hepatectomy (PH) in Wistar and in acetaminofluoren (AAF) pretreated Fisher rats. Sham operated rats were used as controls. Livers were studied at several time points. In the CCl4 model: up to 4 days to reveal acute, and after 15 weeks to reveal chronic damage.

Results: Among the cells isolated from adult rat livers only hepatocytes were Prox1 positive, myofibroblasts, endothelial, Kupffer and hepatic stellate cells were negative. Human hepatoma cells were strongly positive, while MMH cells were negative. Results at protein and RNA levels show higher expression in hepatoma cells than in normal hepatocytes. In CCl4 induced acute liver damage Prox1 was upregulated after 3 and 48 hours. In chronic liver damage its expression did not differ significantly from controls. Prox1 expression was upregulated in PH after 8 hours, but a similar expression pattern was observed in sham operated animals. In the AAF/PH model no significant regulation of Prox1 expression was detected, and there was no Prox1 in gamma-GT positive oval cells in the periportal fields of these livers.

Conclusions: Descriptive and experimental data show that Prox1 is essential during embryonic liver development. It continues to be expressed in regenerating hepatocytes and is upregulated in hepatoma cells. Absence of Prox1 in oval cells challenges the hepatoblastic potential of these cells.

Key words

Prox1 - hepatocyte - hepatoma - liver regeneration