TENASCIN GENE-EXPRESSION IN RAT-LIVER AND IN RAT-LIVER CELLS - INVIVO AND INVITRO STUDIES

Tenascin is a major glycoprotein constituent of the extracellular matrix with a strong affinity to fibronectin; its distribution is believed to be temporarily and spatially limited. Tenascin gene expression is increased during wound healing processes. As repair mechanisms in chronic liver diseases resemble wound healing we studied tenascin gene expression in rat liver and in isolated rat liver cells. In normal rat liver a tenascin specific antiserum stains sinusoidal cells with fiber-like prolongations, which at the same time are desmin-positive (ITO-cells). In the CCl4-acutely-damaged liver a strong tenascin staining is detected in cells located among the mononuclear cells of the inflammatory infiltrates in the areas of necrosis and in cells of the sinusoids. In CCl4-chronically-damaged liver a strong tenascin staining is demonstrable in the connective tissue septa. In both cases, many of the tenascin-positive cells can be identified as desmin-positive by means of the double-staining fluorescence technique. The wall of larger vessels is always tensacin-negative. The staining pattern obtained with a fibronectin-specific antiserum is somewhat comparable with that of tenascin but the vessel wall was positive. Hepatocytes, Kupffer cells, ITO-cells and endothelial cells were isolated from rat liver and studied for their capacity to express the tenascin gene. Biosynthetically labeled tenascin was immunoprecipated from supernatants and cell lysates obtained from cultured ITO-cells and to a much lesser extent from intracellular lysates obtained from endothelial cells; its synthesis in ITO-cells increased during the time in culture. Tenascin was also identified immuno-cytochemically in increasing amount in ITO-cells in culture. We conclude that ITO-cells may play a major role in tenascin synthesis during liver fibrogenesis.