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.