title: Expression and coordinated regulation of matrix metalloproteinases in chronic hepatitis C and hepatitis C virus-induced liver cirrhosis.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany. Lichtinghagen.ralf@mh-hannover.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
authors.forename: Michael
authors.initials: M
authors.lastname: Wehmeier
authors.forename: Dirk
authors.initials: D
authors.lastname: Michels
authors.forename: Christian I
authors.initials: CI
authors.lastname: Haberkorn
authors.forename: Burkhard
authors.initials: B
authors.lastname: Arndt
authors.forename: Peer
authors.initials: P
authors.lastname: Flemming
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Klaus H W
authors.initials: KH
authors.lastname: Boeker
mesh_terms: 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
chemical_list: D004792:Enzyme Precursors; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3