Transforming growth factor alpha (TGF-alpha) expression correlates with DNA replication in regenerating rat liver...

Liver regeneration is a physiological mechanism that leads to restoration of the hepatic parenchyma following hepatectomy or toxic injury. As a two-third hepatectomy is the usual model to analyse this phenomenon, few studies have compared liver regeneration after minor vs major hepatectomy. We have used a quantitative RT-PCR technique to study the hepatic transcription of the TGF-alpha gene in rats submitted to 30% or 80% hepatectomy and we have correlated this transcription with the regenerative response assessed by flow cytometry and Ki-67 expression. The level of TGF-alpha expression and the regenerative response were different, according to the volume of liver removed, and were statistically correlated (r = 0.679, p = 0.002). TGF-alpha expression and phase S peaked at day 2 vs 6 in the 80% vs 30% hepatectomized rat groups, respectively. Ki-67 expression occurred at 2 h post-hepatectomy in the two groups of rats and was observed until day 14 mainly in the 80% hepatectomy group. Our results indicate that TGF-alpha expression in regenerating liver is strongly correlated with hepatocyte mitosis, that a delayed regenerative response occurs following 30% hepatectomy and that the course of regeneration differs between minor vs major hepatectomy.