TGF-β1 Gene Silencing for Treating Liver Fibrosis

被引：94

作者：

Cheng, Kun ^{[1
]}

Yang, Ningning ^{[1
]}

Mahato, Ram I. ^{[1
]}

机构：

[1] Univ Tennessee, Hlth Sci Ctr, Dept Pharmaceut Sci, Memphis, TN 38103 USA

来源：

MOLECULAR PHARMACEUTICS | 2009年 / 6卷 / 03期

关键词：

siRNA; shRNA; transforming growth factor beta 1 (TGF-beta 1); hepatic stellate cells; liver fibrosis; STELLATE CELL ACTIVATION; GROWTH-FACTOR-BETA; TGF-BETA; HEPATIC-FIBROSIS; II RECEPTOR; IN-VIVO; RAT; EXPRESSION; MODEL; RNA;

D O I：

10.1021/mp9000469

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Small interfering RNA (siRNA) and short hairpin RNA (shRNA) targeting different regions of transforming growth factor beta 1 (TGF-beta 1) mRNA were designed and the silencing effect was determined after transfection into immortalized rat liver stellate cells (HSC-T6). There was not only significant decrease in TGF-beta 1, tissue inhibitor of metalloproteinase 1 (TIMP-1), alpha-smooth muscle actin (alpha-SMA) and type 1 collagen after transfection with TGF-beta 1 siRNAs, but also synergism in gene silencing when siRNAs targeting two different start sites were used as a pool for transfection. The two siRNA sequences which efficiently inhibited TGF-beta 1 gene expression were converted to shRNAs via cloning into the pSilencer1.0. There was significant decrease in TGF-beta 1 and TIMP-1 when HSC-T6 cells were transfected with pshRNA targeting the same regions of TGF-beta 1 mRNA as siRNAs. Furthermore, TGF-beta 1 gene silencing in HSC-T6 cells significantly decreased the levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). In conclusion, both siRNA and shRNA showed sequence-specific and dose dependent TGF-beta 1 gene silencing and have the potential to treat liver fibrosis.

引用

页码：772 / 779

页数：8

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