beta-catenin functions as both a structural protein and a transcriptional activator. In this study, we examined the expression of beta-catenin in human cirrhotic livers, and administered adenoviruses carrying the beta-catenin or DeltaTCF4 genes to cirrhotic rats to investigate the role of beta-catenin in the development of liver cirrhosis development. beta-catenin expression was associated with liver cirrhosis development in cirrhotic human and rat liver. beta-catenin adenovirus was capable of accelerating cirrhosis progress but this progression was unaffected by administration of DeltaTCF4 adenovirus. beta-catenin was mainly located in the intercellular regions between liver cells and was highly concentrated in the hepatic sinusoid wall, where alpha-smooth muscle actin (SMA) was also mainly distributed. The binding of beta-catenin to alpha-SMA was also increased in cirrhotic liver. Portal vein blood pressure was significantly increased in the group administered beta-catenin adenovirus, but not in that receiving DeltaTCF4 adenovirus. These results suggest that high concentrations of beta-catenin at the hepatic intercellular membrane and the hepatic sinusoid wall contribute to hepatic hyperpiesia in liver cirrhosis patients. beta-catenin functions as a structural molecule, but not as a signaling molecule, during liver cirrhosis development.
(c) 2009 Wiley-Liss, Inc.