Expression and coordinated regulation of matrix metalloproteinases in chronic hepatitis C and hepatitis C virus-induced liver cirrhosis.
Matrix metalloproteinases (MMPs) are central to tissue remodelling; however, little is known about the temporal pattern and differential regulation of hepatic MMP expression in the course of chronic human liver disease. Using quantitative reverse transcription-PCR ELISA assays, we studied hepatic mRNA expression of MMP-1, -2, -3, -7, -9, -10, -11, -13 and -14 in patients with chronic hepatitis C and hepatitis C virus-induced end-stage liver cirrhosis and controls. Results were compared with histology, hepatic expression of tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3, procollagen types I and IV, laminin, and with circulating protein levels of hyaluronate, TIMP-1 and -2 and MMP proenzymes, as measured by ELISA. The impact of the MMP-3(-1171) promoter polymorphism on hepatic MMP-3 expression was analysed. Hepatic mRNA expression data identified differentially regulated groups of MMPs during the course of chronic hepatitis C, showing either steadily increasing mRNA expression with disease progression (MMP-1, -2, -7 and -14) or transiently elevated expression (MMP-9, -11 and -13). The first group closely correlated to the parameters of fibrogenesis. Hepatic MMP-3 expression was unrelated to disease stage, but was determined by the MMP-3(-1171) promoter polymorphism. In conclusion, MMP expression during the course of chronic hepatitis C appears to be a closely regulated process, with different clusters of coordinately regulated MMP genes being identified.
Lichtinghagen
Ralf
R
Department of Clinical Chemistry, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany. Lichtinghagen.ralf@mh-hannover.de
Bahr
Matthias J
MJ
Wehmeier
Michael
M
Michels
Dirk
D
Haberkorn
Christian I
CI
Arndt
Burkhard
B
Flemming
Peer
P
Manns
Michael P
MP
Boeker
Klaus H W
KH
D016022:Case-Control Studies; D004792:Enzyme Precursors / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000201:enzymology*; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000821:virology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D004792:Enzyme Precursors; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3