Accumulation and cellular localization of fibrinogen/fibrin during short-term and long-term rat liver injury.
OBJECTIVE
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.
Neubauer
K
K
Department of Internal Medicine, Georg-August-University Göttingen, Germany.
Knittel
T
T
Armbrust
T
T
Ramadori
G
G
D000818:Animals; D015152:Blotting, Northern; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D005337:Fibrin; D005340:Fibrinogen; D002251:Carbon Tetrachloride