Comparison of matrix metalloproteinase expression in normal and cirrhotic human liver

To study the extend of ongoing tissue remodelling in end-stage cirrhosis, the expression of different matrix metalloproteinases [interstitial collagenase (MMP-1), Mr 72000 gelatinase (MMP-2), stromelysin-1 (MMP-3) and stromelysin-3 (MMP-11)] and of TIMP-1 was studied in 13 cirrhotic livers explanted...

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Published in:Virchows Archiv : an international journal of pathology 1998-02, Vol.432 (2), p.153-158
Main Authors: LICHTINGHAGEN, R, BREITENSTEIN, K, ARNDT, B, KÜHBACHER, T, BÖKER, K. H. W
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Blotting, Northern
Blotting, Western
Cells, Cultured
Collagenases - biosynthesis
Collagenases - genetics
DNA Primers
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Fibroblasts - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Liver - enzymology
Liver Cirrhosis - enzymology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Middle Aged
Other diseases. Semiology
RNA, Messenger - biosynthesis
Tissue Inhibitor of Metalloproteinase-1 - biosynthesis
Tissue Inhibitor of Metalloproteinase-1 - genetics
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Summary:To study the extend of ongoing tissue remodelling in end-stage cirrhosis, the expression of different matrix metalloproteinases [interstitial collagenase (MMP-1), Mr 72000 gelatinase (MMP-2), stromelysin-1 (MMP-3) and stromelysin-3 (MMP-11)] and of TIMP-1 was studied in 13 cirrhotic livers explanted at transplantation. The results were compared with those obtained in normal liver. Western blot, northern blot, ELISA, RT-PCR and zymogram analysis were used. Proenzymes of stromelysin-1 and -3, interstitial collagenase and Mr 72000 gelatinase were positive in normal liver, while activated enzymes were not detectable in western blot analysis. In cirrhosis proenzyme levels of the studied MMPs were reduced to a mean of 60-70%, but mRNA expression and gelatin-degrading activity increased. TIMP-1 expression was detectable on mRNA level and by ELISA in normal liver and also increased in cirrhosis. Our results show that mRNA expression of certain matrix metalloproteinases is increased in end-stage liver cirrhosis, while the amount of proenzyme is decreased, indicating enhanced MMP proenzyme turnover. These data suggest that besides increased TIMP-1 activity, altered MMP expression may also play a part in fibroproliferation in liver disease.
ISSN:0945-6317
1432-2307
DOI:10.1007/s004280050149