The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis.
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.
Inuzuka
S
S
Second Dept. of Medicine, Kurume University School of Medicine, Japan.
Ueno
T
T
Torimura
T
T
Tamaki
S
S
Sugawara
H
H
Sakata
R
R
Kusaba
N
N
Sata
M
M
Tanikawa
K
K
D000328:Adult; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006525:Hepatitis, Viral, Human / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D016212:Transforming Growth Factor beta; D019096:Vitronectin; D005341:Fibrinolysin