Expression of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from that in normal liver and extrahepatic biliary obstruction

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Abstract
Mucin plays an important role in the development of hepatoliths, which are formed within the intrahepatic large bile ducts. To date, eight apomucins, components of mucin, have been identified. The purpose of this study is to characterize the expression of MUC1, MUC2, MUC3, MUC5, and MUC6 apomucins at both the protein and messenger RNA (mRNA) levels in the intrahepatic large bile ducts and peribiliary glands in 36 livers from patients with hepatolithiasis, in 25 livers from the patients with extrahepatic biliary obstruction, and in 23 histologically-normal livers. MUC3 and MUC6 were constantly and focally expressed, respectively, in the biliary epithelial cells in the intrahepatic large bile ducts in normal livers, extrahepatic biliary obstruction, and, also, hepatolithiasis. In hepatolithiasis, MUC1, MUC2, and MUC5 apomucins were also focally expressed in 33%, 64%, and 89%, respectively, of the large intrahepatic bile ducts examined, whereas such expression was infrequent in normal livers and in extrahepatic biliary obstruction. The markedly proliferated intramural and extramural peribiliary glands in hepatolithiasis frequently expressed MUC3 and MUC6 apomucins and focally expressed MUC2 and MUC5 apomucins. All of the apomucins mRNA expression, except that of MUC1, resembled each protein expression. In conclusion, the characteristics of apomucins in the intrahepatic biliary tree in hepatolithiasis differs from those in normal livers and extrahepatic biliary obstructrion. Increased expression of gel-forming mucins, such as MUC5 and MUC2, could be involved in the formation and development of hepatolithiasis.