Phenotypic change in portal fibroblasts in biliary fibrosis.

Portal fibroblasts have been considered responsible for biliary fibrosis. Since lipocytes show differentiation toward myofibroblast-like cells in hepatic fibrogenesis, we studied whether similar differentiation of portal fibroblasts could be observed in biliary fibrosis. We examined rat livers after bile duct ligation by double immunofluorescent staining of alpha-smooth-muscle actin (alpha-smA) and desmin and also by electronmicroscopy. In the portal tract of normal livers, alpha-smA-positive cells were noted only in the vessel wall, whereas desmin-positive cells were occasionally seen in the connective tissue as well. With the development of biliary fibrosis, alpha-smA was remarkably expressed in the portal connective tissue, while desmin was seen in a small portion of alpha-smA-positive cells around proliferating bile ducts. In normal livers, portal fibroblasts presented quiescent features, such as a small Golgi complex and a few cisternal profiles of endoplasmic reticulum under electron microscopy. After 7 days of bile duct ligation, portal fibroblasts proliferated, were arrayed in multilayers, and were associated with collagen bundles. Some of these fibroblasts had numerous cytoskeletal components, and developed rough endoplasmic reticulum and a dense body. These data suggest that portal fibroblasts appear to differentiate toward myofibroblasts in biliary fibrosis.