Expression And Distribution And Function Of β-catenin In Liver Tissues With Liver Cirrhosis And Hepatocellular Cancer

Liver cirrhosis is the common chronic disease that results in suffusive impairment of liver, which is caused by one or several flbrogenesis pathogens. Hepatocellular carcinoma (HCC) is the primary malignant tumor in our country. A major part of HCCs are the consequence of further development of liver cirrhosis. In this project, we examined the function of B-catenin in liver flbrogenesis development, and try to provide more information to the new treatment strategy on the molecule level.The expression, distribution of B-catenin were analyzed by immuno-histochemical method in the normal liver, cirrhosis liver, liver cirrhosis nearby cancer and hepatocellular cancer. In normal hepatic tissues, weak immunostaining of B-catenin was observed at membranes of the hepatocytes. In the liver cirrhosis tissues, the expression of B -catenin was increased and the expression in the advanced liver cirrhosis was stronger than that in early liver cirrhosis. B-catenin was mainly stained in the membranes and cytosol of the hepatocytes in the cirrhosis tissue nearby cancer. More nuclear distribution was found in HCC than that in liver cirrhosis including cancer nearby cirrhosis tissue. These results suggested that B-catenin might function as a structure adhesion molecule and then transited to a signal transducer during the development of HCC from liver cirrhosis.Double immunofluorescence staining showed B-catenin and actin co-localized under the cell membrane in the lateral of interacted cells in the aggregated cells. Co-immunoprecipitation experiments indicated that p-catenin and a-SMA could interact each other and form a complex in LO2 cells and liver cirrhosis tissues. The results suggested the higher level of B -catenin/ a -SMA complex in liver cirrhosis was associated with the flbrogenesis.In order to confirm the function of 3 -catenin during the development of liver cirrhosis, we established the mouse and rat liver fibrosis model by CCU treatment. The expression level of B-catenin was higher in 90 days model mouse than that in 40 days model mouse. When the recombinative B-catenin adenovirus vector wasadministrationed to liver fibrosis model rat, the expression level of B -catenin increased a lot and most of expressed B -catenin was found on the cell membrane. The portal vein pressure of liver was increased and the portal vein blood stream was decreased in $ -catenin adenovirus infected rat, which suggested that it is the resistance of portal vein responsible for the portal vein pressure increase. HE staining also showed that collagen fibro hyperplasia appeared in B-catenin adenovirus infected rat and the liver architecture was distorted by dense collagen bands in fibrotic liver.Our data reported here indicated that B -catenin is associated with the development of live cirrhosis. The molecular mechanism of its roles during liver cirrhosis development, such as it functions as the structure adherent molecule or signal transducer, still remains to be explored.