Matrix metalloproteinase-13 promotes recovery from experimental liver cirrhosis in rats

Hitoshi Endo, Maki Niioka, Yoshihiko Sugioka, Johbu Itoh, Kaori Kameyama, Isao Okazaki, Risto Ala-Aho, Veli Matti Kähäri, Tetsu Watanabe

Research output: Contribution to journalArticle

36 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)239-252
Number of pages14
JournalPathobiology
Volume78
Issue number5
DOIs
Publication statusPublished - 2011 Sep 1

Keywords

  • Adenoviral gene transfer
  • Extracellular matrix
  • Fibrosis
  • Hepatocyte growth factor
  • Interstitial collagenase
  • Matrix metalloproteinase(s)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Endo, H., Niioka, M., Sugioka, Y., Itoh, J., Kameyama, K., Okazaki, I., Ala-Aho, R., Kähäri, V. M., & Watanabe, T. (2011). Matrix metalloproteinase-13 promotes recovery from experimental liver cirrhosis in rats. Pathobiology, 78(5), 239-252. https://doi.org/10.1159/000328841