| Gene therapy via adenovirus vector carrying matrix metalloproteinase-3 (MMP-3) in a rat model of liver cirrhosis |
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So Yeon Kim, Won Hee Her, Jong Soon Ryu, Jing Sang Wang, Si Hyun Bae, Jeong Won Jang, Chang Wook Kim, Mi Sook Dong, Seung Kew Yoon |
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제약의학회 |
| 원저:간경변 백서 모델에서 아데노바이러스 벡터를 이용한 Matrix Metalloproteinase-3 유전자 치료 |
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김소연, Won Hee Her, Jong Soon Ryu, Jing Sang Wang, Si Hyun Bae, Jeong Won Jang, Chang Wook Kim, Mi Sook Dong, Seung Kew Yoon |
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| Abstract |
Background : Liver cirrhosis is characterized by fibrous scarring and hepatocellular regeneration.
Matrix metalloproteinases (MMPs) comprise a family of zinc-dependent enzymes that degrade the
extracellular matrix (ECM) components. This study examined whether or not gene delivery of human
MMP-3 can attenuate established liver cirrhosis in a rat.
Methods
: Rat liver cirrhosis was induced by an intraperitoneal injection of dimethylnitrosamine
(DMN) three times a week for 8 weeks. The rats were infected once with either a recombinant
adenovirus, AdMMP3.GFP, or a control adenovirus, Ad.GFP, into a portal vein and followed up for
3 weeks. In the rat liver tissues, the collagen content, histopathology and immunohistochemical
staining were measured.
Results
: Liver fibrosis in the DMN induced cirrhotic rat was attenuated along with a diminished
hydroxyproline content and increased dried liver weight after the gene delivery of AdMMP3.GFP. In
addition, the number of activated hepatic stellate cells was lower whereas the proliferation of
hepatocytes, which was confirmed by immunohistochemical staining using anti-proliferating cell
nuclear antigen (PCNA) antibody, was observed in the AdMMP3.GFP infected rats, suggesting that
human MMP-3 stimulated hepatocyte proliferation.
Conclusions
: These results suggest that the gene transfer of human MMP-3 in the liver
attenuates established fibrosis and induces hepatocyte proliferation. Therefore, gene therapy using
MMP-3 in liver cirrhosis might be a promising therapeutic option in the future.(Korean J Med
71:609-619, 2006)
Key Words : Liver cirrhosis, Matrix Metalloproteinase, Gene Therapy, Adenoviruses |
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