Antifibrotic Effect of MMP13-encoding Plasmid DNA Delivered Using Polyethylenimine Shielded With Hyaluronic Acid

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The imbalanced expression of matrix metalloproteinases (MMPs) is associated with liver fibrosis, one of the most common chronic liver diseases. Enhanced expression of MMPs by gene therapy is emerging as a promising antifibrotic strategy, but the effectiveness of this approach depends on reliable systems for delivering MMP genes. Here, we evaluated a newly designed hyaluronic acid (HA)-shielded delivery system for systemic administration of plasmid DNA encoding MMP13 (pMMP13), and tested whether the enhanced expression of MMP13 ameliorates liver fibrosis in mice. In the CCl(4)-induced liver fibrosis model, systemic administration of pMMP13 using HA and polyethylenimine (PEI) significantly increased the expression of MMP13 and reduced collagen deposition. Moreover, following delivery of pMMP13 in a HA-shielded PEI complex, the serum levels of aspartate transaminase were reduced to levels approaching those in untreated normal mice. These results indicate that the delivery of pMMP13 using HA-shielded PEI enhances the efficiency of MMP13 expression in the liver, and highlight the potential of pMMP13 gene therapy as an antifibrotic strategy.
Publisher
Nature Publishing Group
Issue Date
2011-02
Language
English
Article Type
Article
Keywords

LIVER FIBROSIS; GENE DELIVERY; RAT-LIVER; RECEPTOR; ENDOCYTOSIS; EXPRESSION; CYTOTOXICITY; STRATEGIES; THERAPIES; COMPLEXES

Citation

MOLECULAR THERAPY, v.19, no.2, pp.355 - 361

ISSN
1525-0016
DOI
10.1038/mt.2010.262
URI
http://hdl.handle.net/10203/94087
Appears in Collection
BS-Journal Papers(저널논문)
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