Potential role for beta‐catenin in oval cell differentiation during liver injury repair

Abstract

Atypical ductular proliferation (ADP) occurs in the liver following DDC‐induced liver injury. We previously noted a blunted ADP in mice liver lacking β‐catenin after short‐term DDC exposure. To examine whether the 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, but we did observe increased numbers of A6‐positive cells with hepatocyte‐like morphology in TG mice as early as 2 weeks and a dramatic difference at 5 months. These cells may indicate an increased potential for proliferating cells to differentiate in the setting of increased stable β‐catenin. We hypothesized that such a differentiation advantage would allow the liver to recover more quickly following a change from DDC back to a normal diet. Indeed, TG mice exposed to DDC diet for 4 weeks followed by 2 days of normal chow had significantly less A6‐positive cells and had recovered close to normal liver histology compared to what is observed in WT. In sum, these findings indicate diverse roles Wnt/β ‐catenin signaling during oval cell response in mice including a role in the differentiation process during liver repair.