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 deposition 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 deposition in the necrotic pericentral areas of acutely damaged liver tissue after a single CCl4-gavage, whereas in control liver only trace amounts of cellular fibronectin were detectable along the sinusoids. Upon several CCl4-administrations leading to liver fibrosis, cellular fibronectin deposits were accumulated in the fibrotic septa. Northern biot hybridization using a cDNA representing part of the ED-A domain revealed that in liver tissue, in response to an acute intoxication, cellular fibronectin synthesis was initiated within the first 48 h after CCl4-gavage. By in situ hybridisation transcripts for cellular fibronectin were identified in the necrotic areas of acutely damaged tissue restricted to single, pericentrally located cells, whereas no cellular fibronectin 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 intoxication, cellular fibronectin is a member of the accumulating biomatrix and is produced locally by mesenchymal liver cells.