Matrix Metalloproteinase-13 Promotes Recovery from Experimental Liver Cirrhosis in Rats
Matrix Metalloproteinase-13 Promotes Recovery from Experimental Liver Cirrhosis in Rats
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DOI：
10.1159/000328841
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发表时间：
2011-01-01
期刊：
影响因子：
5
通讯作者：
Watanabe, Tetsu
中科院分区：
文献类型：
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作者：
Endo, Hitoshi;Niioka, Maki;Watanabe, Tetsu
目的：探讨基质金属蛋白酶（MMP）-13基因表达在肝纤维化/肝硬化早期恢复过程中的作用。方法：采用四氯化碳（CCl（4））诱导雄性Wistar大鼠肝纤维化模型10周。在最后一次注射CCl（4）后第3天，通过股静脉进行重组腺病毒介导的人MMP-13基因转移（RAdMMP-13）。MMP-13在稳定表达细胞系中的作用也被分析。结果如下：与空载体RAd 66注射大鼠相比，在基因转移后第3天，RAdMMP-13注射大鼠肝脏中的纤维沉积减少。此外，MMP-2和MMP-9的酶活性显着增强在RAdMMP-13注射大鼠的肝脏。在RAdMMP-13注射大鼠中，肝细胞生长因子（HGF）诱导也增加。在建立的稳定的HT-1080细胞转染MMP-13，HGF-α表达和MMP-2和MMP-9酶活性增加。前体HGF向成熟HGF的转化在MMP-13表达细胞系中也增加。结论：通过MMP-13介导的HGF、MMP-2和MMP-9的表达，诱导胶原纤维降解，促进肝再生，强制MMP-13表达有效地加速了肝硬化的恢复。版权所有（C）2011 S. Karger AG，巴塞尔
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