Notch signaling is an evolutionarily conserved mechanism, used to regulate cell 
fate decisions. Four Notch receptors have been identified in man (Notch-1 to 
-4). In this study, semiquantitative reverse transcription polymerase chain 
reaction (RT-PCR) and immunohistochemistry were used to examine the expression 
pattern of Notch receptor genes in whole adult human liver and isolated liver 
cell preparations. All 4 receptors were expressed in the adult liver, with no 
significant differences in the levels of Notch-1, -2, and -4 messenger RNA 
(mRNA) between normal and diseased liver. However, Notch-3 expression appeared 
to be increased in diseased tissue. The distribution of Notch-1 and -4 in normal 
tissue was similar, with Notch-1 also detectable at low levels in the sinusoidal 
endothelium. Notch-2 expression was more widely distributed, and detectable in 
hepatocytes, medium-sized bile ducts, and the sinusoidal endothelium. Notch-3 
expression was seen on hepatocytes, with weaker expression detectable in portal 
veins, hepatic arteries, and the sinusoids. In normal liver tissue Notch-1, -2, 
and -3 were found to be coexpressed on bile duct epithelium; however, with the 
exception of Notch-3 in primary sclerosing cholangitis (PSC) livers, expression 
was absent on proliferating ductules in all disease states examined. 
Interestingly, the expression of Notch-2 and -3 was associated with numerous 
small vessels within the portal tract septa of diseased tissue. The absence of 
Notch receptor expression on proliferating bile ductules and its presence on 
neovessels suggests that Notch signaling may be important for normal bile duct 
formation and the aberrant neovascularization seen in diseased liver tissue.