The Significance of Colocalization of Plasminogen Activator Inhibitor-1 and Vitronectin in Hepatic Fibrosis

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Abstract
Background: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor β1 (TGF-β) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. Methods: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. Results: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TFG-β became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1-VN) decreased. There was a positive correlation between TGF-β and PAI-1, whereas there was a negative correlation between TGF-β and PAI-1VN. Immunoelectron microscopy showed the localization of PAI-1 VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-β 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-β and that it is possible that the plasmin cascade is present in the human liver.