Beta‐catenin regulates proliferation and differentiation of oval cells in mouse liver

Abstract

Atypical ductular proliferation (ADP) occurs in the liver following DDC‐induced liver injury. We noted blunted ADP in mice liver lacking β‐catenin. Also based on the similarities between the processes of ADP in mice and oval cell response in rats, and the role of Wnt/β‐catenin signaling in both events, we sought to examine whether presence of active‐β‐catenin would provide a growth or differentiation advantage to atypical ductular cells in mice. Liver‐specific β‐catenin over expressing mice (TG) with a stabilizing mutation at ser45, were fed the DDC diet. No significant differences in appearance and numbers of A6‐positive cells were observed. Intriguingly, increased numbers of A6‐positive cells with hepatocyte‐like morphology were observed in TG mice. Contrary to short‐term exposure (<4wk) in β‐catenin knockout mice, long‐term exposure to DDC (5 months) led to a significant increase in A6‐positive cells with bridging fibrosis indicating their continued expansion and lack of differentiation. In sum, these findings indicate diverse roles Wnt/β‐catenin signaling during oval cell response in mice.