ACCUMULATION AND CELLULAR-LOCALIZATION OF FIBRINOGEN FIBRIN DURING SHORT-TERM AND LONG-TERM RAT-LIVER INJURY

Background/Aims: During liver fibrosis, there is a putative pacemaker role of fibronectin. Fibrinogen is closely linked to fibronectin during clotting processes. The aim of this study was to show fibrinogen gene expression during liver damage. Methods: Fibrinogen/fibrin deposition in damaged livers was studied by immunohistology. Fibrinogen gene expression was analyzed in vivo in a model of CCl4-induced rat liver damage and in vitro in isolated liver cells by means of Northern blot analysis and in situ hybridization. Results: Immunohistology showed striking amounts of fibrinogen and fibrin deposits in pericentral necrotic areas (short-term damage) and within fibrotic septa (long-term damage). Total RNA extracted from short-term-damaged livers contained an increased fibrinogen messenger RNA level. By in situ hybridization, fibrinogen transcripts were localized in cells of the nonnecrotic areas (short-term damage) and outside fibrotic septa (long-term damage). In vitro studies showed fibrinogen de novo synthesis restricted to hepatocytes. Conclusions: The results show fibrinogen/fibrin deposition during short-term liver injury and liver fibrogenesis, which may suggest the involvement of a ''clotting-like process'' in short-term liver damage and liver fibrosis. The data might indicate that fibrin/fibronectin constitute a ''provisional matrix,'' which affects the attraction and proliferation of inflammatory and matrix-producing cells.