Mechanisms of liver progenitor cell niche activation in canine liver disease

Abstract

In this research project the liver specific progenitor cell (LPC) and its signalling pathways were studied in the dog, by the use of immunohistochemistry. LPC’s play an important role in the ability of the liver to regenerate in response to tissue damage. After activation, LPC’s proliferate (then called reactive ductules) and can differentiate into hepatocytes or cholangiocytes in order to restore the liver’s physiological functions. Much is still unknown about this activation and the signalling pathways involved in this process, making it an interesting subject for research. In this research project we were particularly interested in the Notch and Wnt signalling pathways, since their involvement in the activation of human and rat LPC’s has recently been suggested [14][8]. Initially, immunohistochemistry was performed on paraffin-embedded liver tissue samples. Results showed that the use of paraffin-embedded liver tissue wasn’t satisfying, since outcome of many different staining protocols used varied from negative staining to such high background staining that no conclusions could be drawn from these stainings. In addition, immunohistochemistry was performed on frozen liver tissue samples of different types of liver injury. Results showed increased staining of ß-catenin and thus involvement of Wnt in the proliferation of LPC’s and their differentiation into hepatocytes in acute hepatitis, active cirrhosis, PPVH and possibly extrahepatic bile duct obstruction. Increased staining and thus involvement of Notch-1 in the differentiation of LPC’s into cholangiocytes was seen mainly in active cirrhosis and PPVH. This supports current ideas that Wnt is mainly involved in the proliferation of LPC’s and differentiation into hepatocytes and that Notch-1 is mainly involved in the differentiation of LPC’s into cholangiocytes.