RNA interfering connective tissue growth factor prevents rat hepatic stellate cell activation and extracellular matrix production
文献类型：期刊论文
| 作者 | Li, GM; Li, DG; Xie, Q; Shi, Y; Jiang, S; Jin, YX |
| 刊名 | JOURNAL OF GENE MEDICINE
 |
| 出版日期 | 2008 |
| 卷号 | 10期号:9页码:1039-1047 |
| 关键词 | connective tissue growth factor extracellular matrix hepatic stellate cell liver fibrosis small interfering RNA |
| 通讯作者 | Li, DG (reprint author), Shanghai Jiao Tong Univ, Dept Gastroenterol, Xinhua Hosp, Sch Med, Shanghai 200092, Peoples R China.,dingguo_li@hotmail.com |
| 英文摘要 | Background Connective tissue growth factor (CTGF) is a possible key determinant of progressive fibrosis. Small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally. Therefore, the present study aimed to determine whether synthetic siRNA target CTGF down-regulates the expression of the CTGF gene in primary rat hepatic stellate cells (HSC) and HSC T6, and, furthermore, whether it prevents rat HSC activation and extracelluar matrix (ECM) production. Methods Primary HSC were obtained by enzymatic perfusion of rat liver. HSC T6, primary HSC were treated with siRNAs that target CTGF or a control siRNA by addition to the culture medium. Results We obtained one siRNA that could sequence-specifically reduce target gene expression by over 90% at a concentration of 200 nm in the cell culture medium for a total of three siRNAs targeting CTGF genes. In HSC T6 cells, the effect of CTGF siRNA was dose-dependent (50-200 nM) and time-limited to a 24-72-h period. The siRNA knockdown of CTGF significantly reduced the expression of a-smooth muscle actin protein, increased the number of cells, upregulated the ratios of G0/G1 stage in rat HSC at 7 days of culture after plating, and attenuated the expression of type I and III collagen mRNA with a supernatant concentration of hyaluronic acid, and type III procollagen in an activated HSC of culture for 24-72 h. Conclusions CTGF siRNA could effectively and sequence-specifically down-regulate the expression of CTGF in rat HSC, resulting in significant inhibition of HSC activation and proliferation as well as ECM production. These findings indicate that synthetic siRNA targeting CTGF could prove to be a useful treatment of liver fibrosis. Copyright (C) 2008 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] | LIVER FIBROSIS ; FACTOR EXPRESSION ; TGF-BETA ; MICE ; SIRNA ; INHIBITION ; RESOLUTION ; CIRRHOSIS ; RECEPTOR ; BIOLOGY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000260361600010 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1430]  |
| 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 | Li, GM,Li, DG,Xie, Q,et al. RNA interfering connective tissue growth factor prevents rat hepatic stellate cell activation and extracellular matrix production[J]. JOURNAL OF GENE MEDICINE,2008,10(9):1039-1047. |
| APA | Li, GM,Li, DG,Xie, Q,Shi, Y,Jiang, S,&Jin, YX.(2008).RNA interfering connective tissue growth factor prevents rat hepatic stellate cell activation and extracellular matrix production.JOURNAL OF GENE MEDICINE,10(9),1039-1047. |
| MLA | Li, GM,et al."RNA interfering connective tissue growth factor prevents rat hepatic stellate cell activation and extracellular matrix production".JOURNAL OF GENE MEDICINE 10.9(2008):1039-1047. |
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