Niki T, De Bleser P J, Xu G, Van Den Berg K, Wisse E, Geerts A
Laboratory for Cell Biology and Histology, Faculty of Medicine and Pharmacy, Free University of Brussels, Belgium.
Hepatology. 1996 Jun;23(6):1538-45. doi: 10.1002/hep.510230634.
Fat-storing cells are the major producers of extracellular matrix in the liver. A good immunocytochemical marker is, however, still lacking for this cell type. Desmin, frequently used by most investigators, fails to stain many pericentral fat-storing cells in normal rat liver. The aim of the present study is to evaluate glial fibrillary acidic protein (GFAP) as an alternative marker of fat-storing cells. In normal rat liver, immunostaining of GFAP revealed numerous fat-storing cells with characteristic cytoplasmic extensions. Unlike desmin, which was preferentially expressed in periportal fat-storing cells, GFAP-positive fat-storing cells were distributed more evenly in the lobules. In a narrow periportal zone, however, GFAP-positive cells were occasionally absent. Dual GFAP/desmin staining revealed colocalization of these markers, but fat-storing cells positive only for GFAP or desmin were also present. Chronic carbon tetrachloride exposure induced a spatial change in the expression of GFAP and desmin. At 3 weeks, accumulation of GFAP/desmin double-positive cells was observed in developing fibrotic septa. At 8 weeks, the GFAP positivity in the septa persisted but became weak, while desmin expression became stronger. In contrast, the expression of GFAP within the lobule was gradually decreased as fibrosis progressed. We conclude that GFAP is expressed by a subpopulation of fat-storing cells, which differs partially from the population that expresses desmin. Because in normal rat liver desmin-negative fat-storing cells 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 subsequent downregulation of GFAP in an advanced stage of fibrosis may reflect different stages of fat-storing cell activation. Further investigation is required to determine the functional significance of alteration of GFAP expression in fat-storing cells.
贮脂细胞是肝脏细胞外基质的主要产生者。然而，对于这种细胞类型，仍然缺乏一种良好的免疫细胞化学标志物。大多数研究者常用的结蛋白，无法使正常大鼠肝脏中许多中央周围的贮脂细胞着色。本研究的目的是评估胶质纤维酸性蛋白（GFAP）作为贮脂细胞的一种替代标志物。在正常大鼠肝脏中，GFAP免疫染色显示出许多具有特征性胞质突起的贮脂细胞。与优先在汇管周围贮脂细胞中表达的结蛋白不同，GFAP阳性的贮脂细胞在肝小叶中分布更为均匀。然而，在狭窄的汇管周围区域，偶尔会没有GFAP阳性细胞。GFAP/结蛋白双重染色显示这些标志物共定位，但也存在仅对GFAP或结蛋白呈阳性的贮脂细胞。长期四氯化碳暴露导致GFAP和结蛋白表达发生空间变化。在3周时，在正在形成的纤维化间隔中观察到GFAP/结蛋白双阳性细胞的积累。在8周时，间隔中的GFAP阳性持续存在但变弱，而结蛋白表达变强。相反，随着纤维化进展，肝小叶内GFAP的表达逐渐降低。我们得出结论，GFAP由一部分贮脂细胞表达，这部分细胞与表达结蛋白的细胞群体部分不同。因为在正常大鼠肝脏中，结蛋白阴性的贮脂细胞可通过GFAP染色鉴定，反之亦然，所以GFAP/结蛋白双重染色能更完整地鉴定贮脂细胞。在慢性损伤的肝脏中，GFAP可能不像在正常大鼠肝脏中那样有用。GFAP/结蛋白在正在形成的间隔中共表达以及在纤维化晚期GFAP随后的下调，可能反映了贮脂细胞激活的不同阶段。需要进一步研究以确定贮脂细胞中GFAP表达改变的功能意义。
