Vascularization of the Intrahepatic Biliary Tree and Its Role in the Regulation of Cholangiocyte Growth
The structure of the peribiliary plexus (PBP) in the normal liver has been the subject of a number of studies using both light microscopy, and scanning electron microscopy observations. The PBP, that stems from the hepatic artery branches and flows into the hepatic sinusoids, nourishes the biliary tree and plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium. Little information is available on the rearrangement of the PBP in human liver diseases and in experimental models characterized by proliferation of bile ducts. Bile duct ligation in rats induces marked proliferation of bile ducts. Our group investigated the relationships between proliferation of bile duct cells and peribiliary plexus after common bile duct ligation (BDL) in the rat.
After one week of BDL, a normal organization of the sinusoidal network persists despite significant proliferation of the bile ducts, whereas after three weeks of BDL a typical, well-developed peribiliary plexus is present. The peribiliary plexus runs at the periphery of the liver lobule and consists as bundles of vessels, composed of capillaries of homogeneous diameter with a typical loose round mesh structure. There is no evidence of vascular proliferation or other morphological modifications at the level of sinusoids. Considering the enormous expansion of the PBP during BDL, we evaluated if vascular endothelial growth factor (VEGF) acts as an angiogenic factor in BDL rats. In normal rat livers, VEGF is expressed only in scattered hepatocytes within the periportal zone. As a novel observation, our group observed that in BDL rats, VEGF was expressed by a large number of hepatocytes near the areas of cholangiocyte proliferation, and a strong VEGF immunolocalization was observed in proliferating cholangiocytes. These data were also confirmed in vitro by Western-Blot and RT-PCR analysis. Our findings indicate that the intrahepatic biliary epithelium expresses VEGF particularly during cholangiocyte proliferation. These novel data can be helpful in clarifying the mechanisms triggering the intense vascular proliferative response occurring during BDL.