Overexpression of beta-catenin is responsible for the development of portal hypertension during liver cirrhosis.
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.
Hong
Jian-Jun
JJ
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Pan
Fei-Yan
FY
Qian
Yan
Y
Cheng
Li-Cheng
LC
Zhang
Hong-Xia
HX
Xue
Bin
B
Li
Chao-Jun
CJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051176:beta Catenin; D002251:Carbon Tetrachloride