Homeobox transcription factor Prox1 in rat models of liver damage and regeneration

Aims: Prox1, a homeobox transcription factor, is essential for embryonic liver development, and expressed in hepatoblasts and adult hepatocytes. Changes of Prox1 gene expression in liver damage and regeneration may be of interest to understand hepatocyte origin.

Methods: Prox1 mRNA expression and immunohistochemical protein localisation was examined in normal rat liver and various models of rat liver damage: 1. Acute and chronic liver damage induced by application of carbon-tetra-chloride (CCl₄), 2. Conventional 2/3 partial hepatectomy (PH) 3. PH in combination with 2-acetyl-aminofluorene (AAF) treatment (AAF/PH). Muscular turpentine oil injection and Sham operation was used as acute phase controls. Hepatoblasts were isolated from rat embryos at embryonic days (ED) 12–14.

Results: In normal rat liver Prox1 remained a stable marker of hepatocytes, and was absent from bile ducts. In models of liver damage and regeneration: Prox1 was detectable in hepatocytes and in some scattered cells, which were also positive for OV–6 and cytokeratin 7 (CK–7). Additionally, cells, which were isolated by laser capture from AAF/PH livers expressed alpha-fetoprotein, whereas Prox1 mRNA was not detectable. In models of liver damage and regeneration Prox1 mRNA expression shows a transitional decrease and a restoration period. Isolated rat hepatoblasts (12–14 ED) showed Prox1 and OV–6 immunoreactions.

Conclusions: Prox1 is a stable marker of embryonic hepatoblasts and adult hepatocytes, but could be detected in some adult liver progenitor cells.

Key words

Liver regeneration - Prox1 - liver damage - transcription factor