Matrix metalloproteinase (MMP)-2, MMP-7, and tissue inhibitor of metalloproteinase-1 are closely related to the fibroproliferative process in the liver during chronic hepatitis C.
OBJECTIVE
To study whether expression of matrix metalloproteinases and their inhibitors correlate with ongoing fibrogenesis, we measured hepatic mRNA levels of matrix metalloproteinase (MMP) -2, MMP-7, and MMP-9 as well as tissue inhibitor of metalloproteinase (TIMP) -1, TIMP-2, and TIMP-3 and compared it to histology, procollagen IV alpha-1 chain mRNA levels, and biochemical parameters in patients with chronic active hepatitis C (CAH).


METHODS
Quantitative reverse transcription-polymerase chain reaction/enzyme-linked immunossorbent assay using in vitro transcribed competitor and standard RNA were performed from ten normal livers (N), 29 CAH liver biopsies and seven samples with hepatitis C virus (HCV)-induced end-stage cirrhosis (Ci).


RESULTS
From N to Ci both TIMP and MMP RNA expression increased. However, none of the RNA levels differed significantly between CAH patients with and without fibrosis. Non-parametric correlation analysis and receiver operating characteristics curves show that MMP-2, MMP-7, and TIMP-1 provide the best discrimination between cirrhosis and pre-cirrhotic stages. They also correlate with histologic and biochemical inflammatory activity and with procollagen IV mRNA.


CONCLUSIONS
Hepatic fibroproliferation is associated with alterations of hepatic TIMP and MMP expression. The relation of hepatic TIMP and MMP mRNA levels to disease stage and inflammatory activity underlines their potential as diagnostic markers in chronic liver disease.
Department of Clinical Chemistry, Medizinische Hochschule, Hannover, Germany.
R
R
Lichtinghagen
D
D
Michels
C I
CI
Haberkorn
B
B
Arndt
M
M
Bahr
P
P
Flemming
M P
MP
Manns
K H
KH
Boeker
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D019698:Hepatitis C, Chronic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics
D017931:DNA Primers; D011347:Procollagen; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9