COMPARISON OF GLIAL FIBRILLARY ACIDIC PROTEIN AND DESMIN STAINING IN NORMAL AND CCL4-INDUCED FIBROTIC RAT LIVERS

Fat-storing cells are the major producers of extracellular matrix in t he liver. A good immunocytochemical marker is, however, still lacking for this cell type. Desmin, frequently used by most investigators, fai ls to stain many pericentral fat-storing cells in normal rat liver. Th e aim of the present study is to evaluate glial fibrillary acidic prot ein (GFAP) as an alternative marker of fat-storing cells. In normal ra t liver, immunostaining of GFAP revealed numerous fat-storing cells wi th characteristic cytoplasmic extensions. Unlike desmin, which was pre ferentially expressed in periportal fat-storing cells, GFAP-positive f at-storing cells were distributed more evenly in the lobules, In a nar row periportal zone, however, GFAP-positive cells were occasionally ab sent. Dual GFAP/desmin staining revealed colocalization of these marke rs, but fat-storing cells positive only for GFAP or desmin were also p resent, Chronic carbon tetrachloride exposure induced a spatial change in the expression of GFAP and desmin. At 3 weeks, accumulation of GFA P/desmin double-positive cells was observed in developing fibrotic sep ta. At 8 weeks, the GFAP positivity in the septa persisted but became weak while desmin expression became stronger. In contrast, the express ion of GFAP within the lobule was gradually decreased as fibrosis prog ressed. We conclude that GFAP is expressed by a subpopulation of fat-s toring cells, which differs partially from the population that express es desmin. Because in normal rat liver desmin-negative fat-storing cel ls can be identified by GFAP staining and vice versa, dual GFAP/desmin staining allows more complete identification of fat-storing cells. In chronically injured liver, GFAP may not be as useful as in normal rat liver. The coexpression of GFAP/desmin in developing septa and the su bsequent downregulation of GFAP in an advanced stage of fibrosis may r eflect different stages of fat-storing cell activation. Further invest igation is required to determine the functional significance of altera tion of GFAP expression in fat-storing cells.