Ribozymes against TGF beta 1 reverse character of activated hepatic stellate cells in vitro and inhibit liver fibrosis in rats
文献类型：期刊论文
| 作者 | Song, YH; Chen, XL; Kong, XJ; Liu, NZ; Li, W; Wu, XL; Lin, JS; Jin, YX |
| 刊名 | JOURNAL OF GENE MEDICINE
 |
| 出版日期 | 2005 |
| 卷号 | 7期号:7页码:965-976 |
| 关键词 | gene therapy liver fibrosis RNA catalytic hepatic stellate cell U1 snRNA |
| 通讯作者 | Lin, JS (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,jslin@tjh.tjmu.edu.cn |
| 英文摘要 | Background/aims Transforming growth factor beta(TGF beta 1) is considered the key mediator in the process of liver fibrosis. The purpose of this investigation was to evaluate the activity of ribozymes against TGF beta 1 in a cell-free system and activated hepatic stellate cells (HSCs), and antifibrotic effect in activated HSCs in vitro and in rats. Methods Three ribozymes targeting against TGF beta 1 mRNA were designed, and then cloned into the U1 snRNA expression cassette. The chimeric ribozymes were selected for the analysis of their performances in activated HSCs through the detection of their cleavage activities in a cell-free system. After ribozyme-encoding plasmids had been transfected into HSC-T6 cells, the effects of ribozymes on activated HSCs were evaluated through the analysis of proliferation, activation and collagen deposition of HSC-T6. The adenoviral vector expressing the ribozymes was constructed, and then delivered into rat models of hepatic fibrosis induced by carbon tetrachloride. Results TGF beta 1 expression was efficiently down-regulated inactivated HSCs by U1 snRNA chimeric ribozymes which possessed perfect cleavage activity in a cell-free system. Further studies demonstrated that U1 snRNA chimeric ribozymes inhibited the synthesis of collagen I, reduced deposition of Collagen 1, suppressed BrdU incorporation, but had no effect on desmin and alpha-SMA expression in transfected HSC-T6 cells. Histological analysis demonstrated that the adenoviral vector expressing ribozyme (Rz803) could alleviate fibrotic pathology in rats treated with carbon tetrachloride. Conclusions The anti-TGF beta 1 ribozymes could reverse the character of activated HSCs in vitro and improve fibrotic pathology in vivo. It indicated that TGF beta 1 could be considered as a novel candidate for a therapeutic agent against hepatic fibrosis. Copyright (c) 2005 John Wiley & Sons, Ltd. |
| 学科主题 | Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine |
| 类目[WOS] | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental |
| 关键词[WOS] | GROWTH-FACTOR-BETA ; HUMAN-IMMUNODEFICIENCY-VIRUS ; PRE-MESSENGER-RNA ; INTERFERON-GAMMA ; TGF-BETA ; TRANSCRIPTIONAL ACTIVATION ; EXTRACELLULAR-MATRIX ; COLLAGEN-SYNTHESIS ; GENE-THERAPY ; RECEPTOR |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000230695800014 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1937]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Song, YH,Chen, XL,Kong, XJ,et al. Ribozymes against TGF beta 1 reverse character of activated hepatic stellate cells in vitro and inhibit liver fibrosis in rats[J]. JOURNAL OF GENE MEDICINE,2005,7(7):965-976. |
| APA | Song, YH.,Chen, XL.,Kong, XJ.,Liu, NZ.,Li, W.,...&Jin, YX.(2005).Ribozymes against TGF beta 1 reverse character of activated hepatic stellate cells in vitro and inhibit liver fibrosis in rats.JOURNAL OF GENE MEDICINE,7(7),965-976. |
| MLA | Song, YH,et al."Ribozymes against TGF beta 1 reverse character of activated hepatic stellate cells in vitro and inhibit liver fibrosis in rats".JOURNAL OF GENE MEDICINE 7.7(2005):965-976. |
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