LOCALIZATION AND MESSENGER-RNA STEADY-STATE LEVEL OF CELLULAR FIBRONECTIN IN RAT-LIVER UNDERGOING A CCL(4)-INDUCED ACUTE DAMAGE OR FIBROSIS

In an attempt to investigate cellular fibronectin synthesis and deposi tion during acute liver damage and fibrogenesis, we used the presence of the additional type III-related ED-A domain of cellular fibronectin as a characteristic for distinguishing it from the plasma form. Using site-specific antibodies, we localized cellular fibronectin depositio n in the necrotic pericentral areas of acutely damaged liver tissue af ter a single CCl4-gavage, whereas in control liver only trace amounts of cellular fibronectin were detectable along the sinusoids. Upon seve ral CCl4-administrations leading to liver fibrosis, cellular fibronect in deposits were accumulated in the fibrotic septa. Northern biot hybr idization using a cDNA representing part of the ED-A domain revealed t hat in liver tissue, in response to an acute intoxication, cellular fi bronectin synthesis was initiated within the first 48 h after CCl4-gav age. By in situ hybridisation transcripts for cellular fibronectin wer e identified in the necrotic areas of acutely damaged tissue restricte d to single, pericentrally located cells, whereas no cellular fibronec tin mRNA was detectable in control liver. During fibrogenesis cellular fibronectin transcripts were shown to be synthesized in the immediate vicinity of septa. We conclude that upon acute or chronic intoxicatio n, cellular fibronectin is a member of the accumulating biomatrix and is produced locally by mesenchymal liver cells.