Z Gastroenterol 2005; 43 - 2_12
DOI: 10.1055/s-2005-861625

The Homeobox Transcription Factor Prox1 is Absent from the Induced Oval Cells During Rat Liver Regeneration

J Dudas 1, D Batusic 1, V Cimica 2, M Papoutsi 3, B Saile 1, J Wilting 3, G Ramadori 1
  • 1Abt. Gastroenterologie und Endokrinologie, Uniklinikum Göttingen, Göttingen
  • 2Abteilung für Gastroenterologie und Endokrinologie, Göttingen
  • 3Abt. Pediatrie, Uniklinikum Göttingen, , DeutschlandGöttingen

Aims: In cases of liver injury, when the hepatocytes' ability to repair the damage, is severely held back, this function might be undertaken by undifferentiated progenitor cells, the so-called oval cells. In vitro, under appropriate conditions, these cells might differentiate into both hepatocytes and bile duct epithelial cells. Prox1, a homeobox transcription factor, takes an important role in embryonic liver development, although it remains expressed in hepatocytes of the adult liver as well; but it is absent from the bile duct epithelial cells. In current study Prox1 expression was examined in the oval cells induced in a rat liver regeneration model. Methods: Prox1 expression was studied at RNA and protein levels in livers of Fisher rats sequentially treated with 2-acetyl-aminofluorene (AAF) combined with partial hepatectomy (PH), and in Wistar rats, treated with CCl4 to induce acute or chronic liver damage. The liver tissues were analysed by immunohistochemical, in situ hybridisation, laser capture and PCR methods. Results: Seven days after PH in AAF treated Fisher rats, typical cell dense areas with oval nuclei were detected and have not shown any Prox1 immunoreaction. Both AAF and CCl4 treatments resulted in decrease of Prox1 expression levels, which was later restored, in addition, the AAF treatment needed a longer restoration period. RNA isolated from laser capture sections of the livers of AAF-treated Fisher rats 7 days after PH has shown Prox1 expression in the central liver parenchyma, and α-fetoprotein in the periportal field. In normal rat liver, in acute and chronic CCl4-induced liver damage and in the rat liver regeneration models: Prox1 was exclusively visible in the nuclei of hepatocytes. Conclusions: Our data demonstrate that besides its importance in embryonic liver development, Prox1 remains expressed in hepatocytes even in case of CCl4-induced liver damage, but is completely absent from cells of the biliary epithelial lineage and from oval cells, induced in rat liver regeneration models. Prox1 does not have a regulation role on hepatocyte specific genes like albumin or α-fetoprotein.