Expression of matrix metalloproteinases in spontaneous regression of liver fibrosis.

BACKGROUND/AIMS: Spontaneous regression of liver fibrosis would depend on the degradation of the excessive matrix in the liver. In this study, we tried to determine the kinetics of the expression of genes for matrix metalloproteinase-2 and -13.

METHODOLOGY: Liver fibrosis induced by carbon tetrachloride was resolved after withdrawal of this toxin. Histological staining for fibrous septa and determination of liver collagen content were used to evaluate the extent of liver fibrosis. Expression in liver of matrix metalloproteinase-2 and -13 was determined by reverse transcription-polymerase chain reaction.

RESULTS

The fibrous septa became thinner and interrupted and liver fibrosis resolved rapidly within 10 days. Expression of matrix metalloproteinase-2 and -13 was elevated to 2.5- and 8.7-fold, respectively, at peak fibrosis. The former was maintained at 88%-76% and the later dropped rapidly to 30%-20% in the recovery periods.

CONCLUSIONS

Resolution of liver fibrosis began within 10 days but only to 70%. Gene expression kinetics suggested metalloproteinase-13 might play a more important role in the resolution because it surged more markedly at peak fibrosis and returned to nearly basal levels in the recovery periods in parallel with liver collagen content.