Interactions of β‐catenin with Met & E‐cadherin during Oval Cell Activation.

Abstract

We have previously demonstrated that canonical Wnt/β‐catenin pathway plays a critical role in activation and proliferation of hepatic progenitor cells or oval cells in rats and mice. Here, we investigate if non‐canonical modes of β‐catenin activation play a role in oval cell emergence, expansion or differentiation in rats in the 2‐AAF+PHX models. Confocal microscopy identified Met‐β‐catenin (M‐B) complex apically and E‐cadherin‐β‐catenin (E‐B) on all surfaces in normal hepatocytes. Both these complexes were found on all surfaces in biliary epithelia. In rats treated with 2AAF+PHX, both complexes were observed in oval cells, in a biliary pattern, at 5 days after PHX. However, at 10 days post‐PHX, a clear decrease in both M‐B and E‐B complexes was observed that coincided with nuclear translocation of β‐catenin and active proliferation of oval cells. At 20 days post‐PHX, robust reappearance of both complexes was evident in differentiating oval cells that coincided with decreased β‐catenin activation. Thus, β‐Catenin complex with Met and E‐cadherin undergoes notable modulation during oval cell expansion and during their differentiation into hepatocytes. To conclude, while canonical β‐catenin activation plays a role in oval cell emergence, this is supplemented by noncanonical means during oval cell expansion and differentiation.