Expression of matrix metalloproteinases in spontaneous regression of liver fibrosis.
OBJECTIVE
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.


METHODS
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.
Lee
H S
HS
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Huang
G T
GT
Miau
L H
LH
Chiou
L L
LL
Chen
C H
CH
Sheu
J C
JC
D000818:Animals; D017364:Collagenases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008103:Liver Cirrhosis / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D012075:Remission, Spontaneous; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507081:Mmp13 protein, mouse; C507083:Mmp13 protein, rat; D020778:Matrix Metalloproteinase 2