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- Title
Inhibitory effect of antisense oligonucleotide targeting TIMP-2 on immune-induced liver fibrosis.
- Authors
Qing-He Nie; Chuan-Long Zhu; Ya-Fei Zhang; Jie Yang; Jiu-Cong Zhang; Ren-Tao Gao; Nie, Qing-He; Zhu, Chuan-Long; Zhang, Ya-Fei; Yang, Jie; Zhang, Jiu-Cong; Gao, Ren-Tao
- Abstract
<bold>Introduction: </bold>We previously reported that both experimental and human studies have shown the importance of TIMP-1 and TIMP-2 in the development of liver fibrosis, a disease mostly caused by HBV and HCV infection in China. Inhibiting the expression of TIMP-1 by an antisense oligonucleotide (ASON) can prevent liver fibrosis through decreasing the deposition of collagen I and III. Whether blocking the expression of TIMP-2 has the same effect on liver fibrosis is not clear.<bold>Materials and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
ANTISENSE nucleic acids; OLIGONUCLEOTIDES; FIBROSIS; METALLOPROTEINASES; GENE therapy; LABORATORY rats; ANIMAL experimentation; COLLAGEN; COMPARATIVE studies; ENZYME-linked immunosorbent assay; HIGH performance liquid chromatography; CIRRHOSIS of the liver; RESEARCH methodology; MEDICAL cooperation; NONPARAMETRIC statistics; NUCLEOTIDES; POLYMERASE chain reaction; PROTEINS; RATS; RESEARCH; STATISTICAL sampling; SERUM albumin; WESTERN immunoblotting; EVALUATION research; REVERSE transcriptase polymerase chain reaction; DISEASE progression; METABOLISM; PREVENTION
- Publication
Digestive Diseases & Sciences, 2010, Vol 55, Issue 5, p1286
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-009-0858-5