Increased oval cell response and fibrosis in beta‐catenin null livers after long‐term DDC exposure

Abstract

An oval cell response, or ductular reaction, occurs in the mouse liver following DDC‐induced liver injury. We previously reported a potential role for β‐catenin in oval cell induction and expansion. After short term exposure (2‐4 weeks) to DDC, β‐catenin knockout liver had less A6‐positive oval cells than wild type liver. To examine the role of β‐catenin in the response to long‐term injury, we exposed WT and KO mice to DDC for 5 months. The livers from these animals were examined histologically to examine the extent of biliary injury and oval cell response. At 5 months in both groups of animals we observed the emergence of cells with scant cytoplasm and oval‐shaped nuclei, but this response was more dramatic in the KO. We utilized the oval cell marker A6 to compare the response between the two groups. Contrary to short‐term exposure (<4wk), KO liver harbored significantly more A6 positive cells than WT. This coincided with more fibrosis in the KO than observed in WT liver. We also observed nodular formation upon macroscopic examination of the KO liver. These likely indicate continued expansion and lack of differentiation of oval cells in this model. In sum, these findings indicate diverse roles for Wnt/β ‐catenin signaling during oval cell response in mice.