Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid

Eun Joong Kim; Hee Jeong Cho; Daeui Park; Ji Yeon Kim; Young Bong Kim; Tae Gwan Park; Chang Koo Shim; Yu Kyoung Oh

doi:10.1038/mt.2010.262

Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid

Eun Joong Kim, Hee Jeong Cho, Daeui Park, Ji Yeon Kim, Young Bong Kim, Tae Gwan Park, Chang Koo Shim, Yu Kyoung Oh

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

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.

Original language	English
Pages (from-to)	355-361
Number of pages	7
Journal	Molecular Therapy
Volume	19
Issue number	2
DOIs	https://doi.org/10.1038/mt.2010.262
State	Published - Feb 2011
Externally published	Yes

Funding

This work was supported by the research grants from the Korean Health Technology R&D project (A090945), Ministry for Health, Welfare, and Family Affairs, and from National Research Laboratory (ROA-2006-000-10290-0), South Korea.

Funders	Funder number
Ministry for Health, Welfare, and Family Affairs
National Research Laboratory	ROA-2006-000-10290-0

Access to Document

10.1038/mt.2010.262

Cite this

@article{923ab87af92d43879953624963f096ed,

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.",

author = "Kim, {Eun Joong} and Cho, {Hee Jeong} and Daeui Park and Kim, {Ji Yeon} and Kim, {Young Bong} and Park, {Tae Gwan} and Shim, {Chang Koo} and Oh, {Yu Kyoung}",

year = "2011",

month = feb,

doi = "10.1038/mt.2010.262",

language = "English",

volume = "19",

pages = "355--361",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid

AU - Kim, Eun Joong

AU - Cho, Hee Jeong

AU - Park, Daeui

AU - Kim, Ji Yeon

AU - Kim, Young Bong

AU - Park, Tae Gwan

AU - Shim, Chang Koo

AU - Oh, Yu Kyoung

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79551615156&partnerID=8YFLogxK

U2 - 10.1038/mt.2010.262

DO - 10.1038/mt.2010.262

M3 - Article

AN - SCOPUS:79551615156

SN - 1525-0016

VL - 19

SP - 355

EP - 361

JO - Molecular Therapy

JF - Molecular Therapy

IS - 2

ER -

Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this