The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis.

Abstract:

BACKGROUND:We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) 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 TGF-beta 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-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating 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 human liver.

journal_name

Scand J Gastroenterol

authors

Inuzuka S,Ueno T,Torimura T,Tamaki S,Sugawara H,Sakata R,Kusaba N,Sata M,Tanikawa K

doi

10.3109/00365529709011224

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

1052-60

issue

10

eissn

0036-5521

issn

1502-7708

journal_volume

32

pub_type

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