TGF-beta1 gene silencing for treating liver fibrosis.
TGF-beta1 gene silencing for treating liver fibrosis.
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DOI：
10.1021/mp9000469
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发表时间：
2009-05
影响因子：
4.9
通讯作者：
Mahato RI
中科院分区：
文献类型：
--
作者：
Cheng K;Yang N;Mahato RI
设计针对转化生长因子β1（TGF-β1）mRNA不同区域的小干扰RNA（siRNA）和短发夹RNA（shRNA），转染永生化大鼠肝星状细胞（HSC-T6），观察其沉默效果。TGF-β1 siRNA转染后，TGF-β1、TIMP-1、α-SMA和I型胶原表达均显著降低，且以两个不同起始位点的siRNA作为转染池时，基因沉默作用具有协同效应。通过克隆到pSilencer1.0中，将有效抑制TGF-β1基因表达的两个siRNA序列转化为shRNA。当转染与siRNA靶向相同区域的pshRNA后，HSC-T6细胞中TGF-β1和TIMP-1的表达显著降低。此外，HSC-T6细胞中TGF-β1基因沉默显著降低炎性细胞因子如肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1β）的水平。结论：siRNA和shRNA均具有序列特异性和剂量依赖性的TGF-β1基因沉默作用，具有治疗肝纤维化的潜力。
Small interfering RNA (siRNA) and short hairpin RNA (shRNA) targeting different regions of transforming growth factor β1 (TGF-β1) 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-β1, tissue inhibitor of metalloproteinase 1 (TIMP-1), α-smooth muscle actin (α-SMA) and type I collagen after transfection with TGF-β1 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-β1 gene expression were converted to shRNAs via cloning into the pSilencer1.0. There was significant decrease in TGF-β1 and TIMP-1 when HSC-T6 cells were transfected with pshRNA targeting the same regions of TGF-β1 mRNA as siRNAs. Furthermore, TGF-β1 gene silencing in HSC-T6 cells significantly decreased the levels of inflammatory cykokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). In conclusion, both siRNA and shRNA showed sequence-specific and dose dependent TGF-β1 gene silencing, and has the potential to treat liver fibrosis.
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影响吡啶鎓脂质基因转移的结构和配方因素。
影响因子：
4.7
作者：
Zhu L;Lu Y;Miller DD;Mahato RI
通讯作者：
Mahato RI
DOI：
10.1016/j.bbrc.2006.03.087
发表时间：
2006-05-19
影响因子：
3.1
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Kim, KH;Kim, HC;Park, KK
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DOI：
10.1097/00042737-200402000-00001
发表时间：
2004-02-01
影响因子：
2.1
作者：
Shek, FW;Benyon, RC
通讯作者：
Benyon, RC
DOI：
10.1073/pnas.96.22.12719
发表时间：
1999-10-26
影响因子：
11.1
作者：
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通讯作者：
Bissell, DM
DOI：
10.1073/pnas.96.5.2345
发表时间：
1999-03-02
影响因子：
11.1
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Qi, Z;Atsuchi, N;Ueno, H
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Ueno, H