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.