title: Matrix metalloproteinase-13 promotes recovery from experimental liver cirrhosis in rats.
abstract: OBJECTIVE
  To evaluate the role of matrix metalloproteinase (MMP)-13 gene expression in the early phase of recovery from liver fibrosis/cirrhosis.
  
  
  METHODS
  Liver fibrosis was induced in male Wistar rats by administration of carbon tetrachloride (CCl(4)) for 10 weeks. Recombinant adenovirus-mediated human MMP-13 gene transfer (RAdMMP-13) was performed via the femoral vein on day 3 after the last CCl(4) injection. The role of MMP-13 in stably expressing cell lines was also analyzed.
  
  
  RESULTS
  Fibrous deposition in the liver was decreased in RAdMMP-13-injected rats by day 3 after gene transfer compared with empty vector RAd66-injected rats. Furthermore, MMP-2 and MMP-9 enzymatic activity was markedly enhanced in the liver of RAdMMP-13 injected rats. Hepatocyte growth factor (HGF) induction was also increased in RAdMMP-13 injected rats. In established stable HT-1080 cells transfected with MMP-13, HGF-α expression and MMP-2 and MMP-9 enzymatic activity were increased. The conversion of precursor HGF into mature HGF was also increased in the MMP-13 expressing cell lines.
  
  
  CONCLUSIONS
  Forced MMP-13 expression effectively accelerated recovery from liver cirrhosis via the effects of MMP-13-mediated HGF, MMP-2, and MMP-9 expression, which induced the degradation of collagen fibers and promoted hepatic regeneration.
authors.affiliation: Center for Molecular Prevention and Environmental Medicine, Department of Community Health, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endo
authors.forename: Maki
authors.initials: M
authors.lastname: Niioka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sugioka
authors.forename: Johbu
authors.initials: J
authors.lastname: Itoh
authors.forename: Kaori
authors.initials: K
authors.lastname: Kameyama
authors.forename: Isao
authors.initials: I
authors.lastname: Okazaki
authors.forename: Risto
authors.initials: R
authors.lastname: Ala-Aho
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kähäri
authors.forename: Tetsu
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015971:Gene Expression Regulation, Enzymologic; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D017228:Hepatocyte Growth Factor; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9