Laminin alpha-3 and thrombospondin-1 differently regulate the survival and differentiation of hepatocytes and hepatic stem cells from neonatal mice.

The aim of this study was to search and identify the extracellular matrix/adhesion molecules potentially regulating liver regeneration. By using pathway-focused PCR array, we investigated the dynamic changes in the expression of extracellular matrix and adhesion molecules in normal livers or cholestatic livers following partial hepatectomy in adult mice. To confirm the data from PCR array, we further evaluated how laminin alpha-3 and thrombospondin-1 mediate the survival and differentiation of matured hepatocytes and immature hepatic stem cells by using primarily isolated liver cells from neonatal mice. According to the different changes in the expression of extracellular matrix and adhesion molecules between normal livers and cholestatic livers, we could find a number of potential molecules involved in liver regeneration. Our in vitro evaluations indicated that laminin alpha-3 significantly increased the number of liver cells (P<0.01 vs. Control) but decreased the proportion of claudin-3-positive hepatic stem cells (P<0.05 vs. Control). In contrast, thrombospondin-1 significantly reduced cell apoptosis (P<0.05 vs. Control) and maintained the proportion of claudin-3-positive hepatic stem cells. Otherwise, the combination of laminin alpha-3 and thrombospondin-1 increased the proliferation of liver cells. Based on our data, laminin alpha-3 and trombospondin-1 differently regulate the survival and differentiation of hepatocytes and hepatic stem cells, but relevant mechanisms are required to be elucidated by further study. AJTR