Phenotypic modulation in lipocytes in experimental liver fibrosis

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Abstract
The presence of a‐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 a‐smA‐positive cells and lipocytes has not been determined. The biological implication of a‐smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a‐smA and desmin (a marker for lipocytes), or a‐smA and collagen, and double immunohistochemical staining of a‐smA and 5‐bromo‐2′‐deoxyuridine (BrdUrd) in carbon tetrachloride‐induced fibrotic rat livers. In normal and control livers, a‐smA‐positive cells were not seen in the lobules, whereas scattered desmin‐positive cells were present. With the development of hepatic fibrosis, a‐smA was expressed only in a portion of desmin‐positive cells located predominantly around collagen bundles. A number of a‐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 a‐smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a‐smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.