It is worthy of note that HPCs were found mainly in the proliferating bile ductules, defined as oval cell ductules of the biliary tree, where they formed periportal ductular structures representing an extension of the canals of Hering (Figures 2(a) and 2(b)).
In all experimental groups, along with the onset and development of fibrogenesis, the populations of the activated hepatic stellate cells, including transitional HSCs, were frequently observed near the proliferating bile ductules or very close to isolated HPCs at the edge of regenerative nodules and in the fibrous septa (Figures 1(c), 1(d), 1(e), 1(f), 2(c), 2(d), 3(a), 3(b), 3(c), and 3(d)).
Interestingly, we found that the activated HSCs observed in the current study were always intimately associated with proliferating or mature bile ductules as well as with scattered hepatic oval cells present in the already developed or being formed fibrotic foci.
It should be noted that TEM analysis showed clearly a very rare phenomenon of penetration by cytoplasmic processes sent by activated HSCs, the basement membrane of bile ductules, and formation of direct cell-cell contact with ductular epithelial cells related to progenitor/oval cells.
The HPCs, apart from their major location within the neoforming bile ductules, were also found in the form of isolated oval cells in periportal connective tissue, in the already developed or being formed fibrotic foci and at the periphery of regenerative nodules.
Previously, we have reported the specific distribution of pS9GSK3[beta] in normal tissues, such as intestinal crypt, bile ductules
of the liver, pancreatic ductal and centroacinar cells, distal nephron of the kidney, urothelium, lung, and mesothelial cells , which is strikingly in accordance with p-mTOR expression shown in this study.