Overexpression of β-Catenin is Responsible for the Development of Portal Hypertension During Liver Cirrhosis

β-catenin functions as both a structural protein and a transcriptional activator. In this study, we examined the expression of β-catenin in human cirrhotic livers, and administered adenoviruses carrying the β-catenin or ΔTCF4 genes to cirrhotic rats to investigate the role of β-catenin in the development of liver cirrhosis development. β-catenin expression was associated with liver cirrhosis development in cirrhotic human and rat liver. β-catenin adenovirus was capable of accelerating cirrhosis progress but this progression was unaffected by administration of ΔTCF4 adenovirus. β-catenin was mainly located in the intercellular regions between liver cells and was highly concentrated in the hepatic sinusoid wall, where α-smooth muscle actin (SMA) was also mainly distributed. The binding of β-catenin to α-SMA was also increased in cirrhotic liver. Portal vein blood pressure was significantly increased in the group administered β-catenin adenovirus, but not in that receiving ΔTCF4 adenovirus. These results suggest that high concentrations of β-catenin at the hepatic intercellular membrane and the hepatic sinusoid wall contribute to hepatic hyperpiesia in liver cirrhosis patients. β-catenin functions as a structural molecule, but not as a signaling molecule, during liver cirrhosis development. Anat Rec, 292:818–826, 2009. © 2009 Wiley-Liss, Inc.