THE SIGNIFICANCE OF COLOCALIZATION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND VITRONECTIN IN HEPATIC-FIBROSIS

Background: We examined the relationships among vitronectin (VN), plas minogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta) in liver diseases to evaluate the presence of plasmi n cascade in human hepatic fibrosis. Methods: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 an tigen, and PAI-1 activity levels were evaluated. Biopsied liver specim ens were observed by light and electron microscopy after immunohistoch emical staining. Morphometric analysis was performed on these specimen s. Results: Plasma. VN and PAI-1 activity levels decreased significant ly with the progression of hepatic fibrosis and were particularly mark ed in the liver cirrhosis group. Plasma PAI-I antigen level increased significantly. The immunolocalization of the active form of TFG-beta b ecame more intense with the progression of hepatic fibrosis, whereas t hat of the dual-stained positive areas of PAI-I and VN (PAI-I VN) decr eased. There was a positive correlation between TGF-beta and PAI-1, wh ereas there was a negative correlation between TGF-beta and PAI-1-VN. Immunoelectron microscopy showed the localization of PAI-1 VN in the e xtracellular space around the sinusoidal cells or surface of aggregati ng platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. Conclusions: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the hum an liver.