Matrix Metalloproteinase-13 Promotes Recovery from Experimental Liver Cirrhosis in Rats

被引：63

作者：

Endo, Hitoshi ^{[1
]}

Niioka, Maki ^{[2
]}

Sugioka, Yoshihiko ^{[3
]}

Itoh, Johbu ^{[2
]}

Kameyama, Kaori ^{[4
]}

Okazaki, Isao ^{[5
]}

Ala-Aho, Risto ^{[6
,7
,8
]}

Kahari, Veli-Matti ^{[6
,7
,8
]}

Watanabe, Tetsu ^{[1
]}

机构：

[1] Tokai Univ, Ctr Mol Prevent & Environm Med, Dept Community Hlth, Sch Med, Isehara, Kanagawa 2591193, Japan

[2] Tokai Univ, Teaching & Res Support Ctr, Sch Med, Isehara, Kanagawa 2591193, Japan

[3] Asahikawa Med Coll, Dept Hlth Sci, Asahikawa, Hokkaido 078, Japan

[4] Keio Univ, Sch Med, Dept Pathol, Tokyo 160, Japan

[5] Int Univ Hlth & Welf, Sanno Hosp, Dept Internal Med, Tokyo, Japan

[6] Univ Turku, Dept Dermatol, Turku, Finland

[7] Univ Turku, MediCity Res Lab, Turku, Finland

[8] Turku Univ Hosp, FIN-20520 Turku, Finland

来源：

PATHOBIOLOGY | 2011年 / 78卷 / 05期

基金：

芬兰科学院;

关键词：

Fibrosis; Matrix metalloproteinase(s); Interstitial collagenase; Adenoviral gene transfer; Extracellular matrix; Hepatocyte growth factor; HEPATOCYTE GROWTH-FACTOR; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; HEPATIC-FIBROSIS; INTERSTITIAL COLLAGENASE; PARTIAL-HEPATECTOMY; FACTOR ACTIVATION; CELLS; INHIBITORS; RESOLUTION;

D O I：

10.1159/000328841

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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

引用

页码：239 / 252

页数：14

共 48 条

[1] Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells [J].