Abstract | INTRODUCTION: MATERIALS AND METHODS: To interfere with this potentially effective target, we designed and synthesized two different ASON targeting TIMP-2, then mixed and transfected them by hydrodynamic injection into the rat livers with immune-induced liver fibrosis. We isolated HSCs from the HSA-induced rat model with liver fibrosis, and transfected them with ASON or sense oligonucleotide in vitro. RESULTS: We observed that TIMP-2 ASON markedly reduced the expression of TIMP-2 by real-time PCR, Western blot, and enzyme linked immunosorbent assay. However, TIMP-2 ASON had little effect on alpha-SMA expression in vitro by Western blot. Inhibition of the expression of TIMP-2 by TIMP-2 ASON clearly decreased deposition of collagen I and IV, ameliorated liver pathology, and improved the liver function among the rats with immune-induced liver fibrosis. CONCLUSION: The results suggested that TIMP-2 ASON could prevent the progression of liver fibrosis in this rat model. It is possible that this could form the basis for exploration of new liver anti- fibrosis drugs at a genetic level.
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Authors | Qing-He Nie, Chuan-Long Zhu, Ya-Fei Zhang, Jie Yang, Jiu-Cong Zhang, Ren-Tao Gao |
Journal | Digestive diseases and sciences
(Dig Dis Sci)
Vol. 55
Issue 5
Pg. 1286-95
(May 2010)
ISSN: 1573-2568 [Electronic] United States |
PMID | 19517234
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Oligonucleotides, Antisense
- Serum Albumin
- Tissue Inhibitor of Metalloproteinase-2
- Collagen
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Topics |
- Animals
- Blotting, Western
- Chromatography, High Pressure Liquid
- Collagen
(metabolism)
- Disease Progression
- Enzyme-Linked Immunosorbent Assay
- Female
- Genetic Therapy
(methods)
- Liver Cirrhosis
(immunology, prevention & control)
- Oligonucleotides, Antisense
(genetics, pharmacology)
- Random Allocation
- Rats
- Rats, Wistar
- Reverse Transcriptase Polymerase Chain Reaction
- Serum Albumin
- Statistics, Nonparametric
- Tissue Inhibitor of Metalloproteinase-2
(genetics)
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