期刊
PATHOBIOLOGY
卷 78, 期 5, 页码 239-252出版社
KARGER
DOI: 10.1159/000328841
关键词
Fibrosis; Matrix metalloproteinase(s); Interstitial collagenase; Adenoviral gene transfer; Extracellular matrix; Hepatocyte growth factor
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Academy of Finland [114409, 130224]
- Finnish Cancer Research Foundation
- Sigrid Juselius Foundation
- Turku University Hospital
- Cancer Foundation Finland sr [110087, 100104] Funding Source: researchfish
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-alpha 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. Copyright (C) 2011 S. Karger AG, Basel
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