Tissue inhibitor of metalloproteinase-1 in the liver of patients with chronic liver disease.
OBJECTIVE
Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. The relationship between serum and liver levels of TIMP-1 was also examined in some patients.


METHODS
The subjects were 68 patients who underwent liver biopsy. The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidine.


RESULTS
As compared with the controls (n=10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A patients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1-fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease.


CONCLUSIONS
Liver TIMP-1 concentration increases with progression of the liver disease, when the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis.
Murawaki
Y
Y
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Ikuta
Y
Y
Idobe
Y
Y
Kitamura
Y
Y
Kawasaki
H
H
D000328:Adult; D000704:Analysis of Variance; D001706:Biopsy; D002908:Chronic Disease; D005234:Fatty Liver / Q000097:blood / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood; D006506:Hepatitis A / Q000097:blood / Q000473:pathology; D006509:Hepatitis B / Q000097:blood / Q000473:pathology; D006521:Hepatitis, Chronic / Q000097:blood / Q000473:pathology; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011480:Protease Inhibitors / Q000032:analysis*; D012016:Reference Values; D012044:Regression Analysis; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases