PHENOTYPIC MODULATION IN LIPOCYTES IN EXPERIMENTAL LIVER FIBROSIS

The presence of alpha-smooth muscle actin (smA)-positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the alpha-smA-positive cells and lipocytes has not been determined. The biological implication of alpha-smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of alpha-smA and desmin (a marker for lipocytes), or alpha-smA and collagen, and double immunohistochemical staining of alpha-smA and 5-bromo-2'-deoxyuridine (BrdUrd) in carbon tetrachloride-induced fibrotic rat livers. In normal and control livers, alpha-smA-positive cells were not seen in the lobules, whereas scattered desmin-positive cells were present. With the development of hepatic fibrosis, alpha-smA was expressed only in a portion of desmin-positive cells located predominantly around collagen bundles. A number of alpha-smA-positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast-like cells, since alpha-smA is expressed with desmin in myofibroblasts in scar tissue. The expression of alpha-smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.