title: Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Kim
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D015151:Immunoblotting; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000628:therapy*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry*; D016133:Polymerase Chain Reaction
chemical_list: D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride; D053509:Matrix Metalloproteinase 13