Glial fibrillary acidic protein as a marker of perisinusoidal stellate cells that can distinguish between the normal and myofibroblast-like phenotypes

Abstract

Glial fibrillary acidic protein (GFAP) has recently been shown to provide a marker for normal perisinusoidal stellate cells (PSC) in the liver. However, nothing was known so far about the changes in the intercellular abundancy of GFAP during transformation of PSC into myofibroblasts, a process characterized by marked changes in the expression of elements of the cytoskeleton. In order to address this question, we have used double-labelling immunofluorescence techniques for detecting smooth muscle alpha-actin (SMAA) and the intermediate filament proteins, GFAP, desmin and vimentin, taking advantage of the fact that PSC present in primary cultures of rat hepatocytes proliferate and transform. GFAP and vimentin were expressed in PSC throughout cultivation, while desmin which stained only about half of the PSC in early cultures was expressed in all GFAP-positive cells later on. The intensity of staining for GFAP in PSC transiently increased till the second day of cultivation followed by a decrease. At the 6th day of cultivation, staining for GFAP was seen only in the perinuclear region and as a faint rim at the contours of the cells. In contrast, SMAA, an established marker for transformed PSC, started to be expressed at the third day. Thereafter, immunoreactivity for SMAA increased continuously, indicating an inverse expression of GFAP and SMAA during transformation. These results indicate that GFAP, due to the plasticity of its expression, can discriminate between the normal untransformed and transformed phenotypes of PSC. Furthermore, they suggest a role of GFAP not only as a reliable marker, but also in the maintenance and/or function of the normal differentiated phenotype of liver PSC.