RNA interference targeting the platelet‐derived growth factor receptor β subunit ameliorates experimental hepatic fibrosis in rats

Chen, Siwen; Zhang, Xingrong; Wang, Chong-Ze; Chen, Weizhong; Xie, Wei‐Fen; Chen, Yue-Xiang

doi:10.1111/j.1478-3231.2008.01759.x

Cited by 39 publications

(26 citation statements)

References 29 publications

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“…TGF-b and platelet-derived growth factor are known to be highly expressed by fibrotic liver 189,222,223 and to induce myofibroblast differentiation in MSCs. 47 Human MSCs were shown to have the ability to respond to TGF-b 224 and were found to proliferate in the presence of this growth factor.…”

Section: Msc Contribution To Liver Fibrogenic Processmentioning

confidence: 99%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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Mesenchymal stem (stromal) cells (MSCs) are a source of circulating progenitors that are able to generate cells of all mesenchymal lineages and to cover cellular demands of injured tissues. The extent of their transdifferentiation plasticity remains controversial. Cells with MSC properties have been obtained from diverse tissues after purification and expansion in vitro. These cellular populations are heterogeneous and under certain conditions show pluripotent-like properties. MSCs present immunosuppressive and anti-inflammatory features and high migratory capacity toward inflamed or remodeling tissues. In this study we review available data regarding factors and signaling axes involved in the chemoattraction and engraftment of MSCs to an injured tissue or to a tissue undergoing active remodeling. Moreover, experimental evidence in support of uses of MSCs as vehicles of therapeutic genes is discussed. Because of its regenerative capacity and its particular immune properties, the liver is a good model to analyze the potential of MSCbased therapies. Finally, the potential application of MSCs and genetically modified MSCs in liver fibrosis and hepatocellular carcinoma (HCC) is proposed in view of available evidence.

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Section: Msc Contribution To Liver Fibrogenic Processmentioning

confidence: 99%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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“…Targeted molecular therapy is a novel therapeutic strategy for GBM (18). In previous studies, targeting of PDGFR using selected inhibitors achieved some success in the treatment of gliomas.…”

Section: Discussionmentioning

confidence: 99%

“…The short hairpin (sh)RNA corresponding to the 6-nucleotide loop sequence (CTC GAG) of the PDGFR-β-siRNA, and its negative control containing the 9-nucleotide loop sequence (TTC AAG AGA) flanked by sense and antisense siRNA sequences, were synthesized by polymerase chain reaction (PCR) as previously described (18). The PDGFR-β-shRNA was inserted immediately into the shRNA expression system of the pU6-vshRNA-UBI-GFP vector (Shanghai GeneChem Co., Ltd.) to generate an RNAi-PDGFR-β vector, in which PDGFR-β shRNA was driven by the LV promoter and green fluorescent protein (GFP) was the reporter gene.…”

Section: Construction and Transfection Of The Rnai-pdgfr-β Vectormentioning

confidence: 99%

Silencing platelet-derived growth factor receptor-β enhances the radiosensitivity of C6 glioma cells in vitro and in vivo

et al. 2017

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Abstract. Platelet-derived growth factor receptor (PDGFR)-β is an important tyrosine kinase and its downregulation has been reported to alter the radiosensitivity of glioma cells, although the underlying mechanism is unclear. In order to investigate the effect of PDGFR-β on the radiosensitivity of glioblastoma, the present study transfected C6 glioma cells with a PDGFR-β-specific small interfering (si)RNA expression plasmid, and downregulation of the expression of PDGFR-β in C6 glioma cells was confirmed by western blotting and immunohistochemical analysis. Clone formation assays and xenograft growth curves demonstrated that PDGFR-β-siRNA enhanced the radiosensitivity of C6 glioma cells in vitro and in vivo. Furthermore, MTT and xenograft growth curves demonstrated that PDGFR-β-siRNA inhibited the proliferation of C6 glioma cells in vitro and in vivo, and terminal deoxynucleotidyl transferase dUTP nick end-labeling and immunohistochemical analyses demonstrated that PDGFR-β-siRNA induced apoptosis and inhibited the expression of Ki-67, cyclin B1 and vascular endothelial growth factor in C6 glioma cell xenografts. Taken together, these results suggested that PDGFR-β may be used as a target for the radiosensitization of glioblastoma.

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“…The specific sequence is used to target messenger RNA (mRNA) and mediate its degradation. Therefore, the level of protein encoded by the mRNA is reduced . Since RNAi‐mediated gene silencing has also been shown to be effective in mammalian cells, an RNAi technology that can be used to treat human diseases has become possible.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of RNA interference targeting Ikkβ on hepatic fibrosis in rats

Wei

Sun

Zhou

et al. 2019

J of Cellular Biochemistry

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Nuclear factor‐κB (NF‐κB) is an important regulatory factor in cells. NF‐κB has a wide range of biological activities. After activation, it participates in the transcription and regulation of many genes and plays a role in infection, inflammatory response, oxidative stress, cell multiplication, and apoptosis. The activation of the NF‐κB signal pathway is dependent on the degradation of the IκB kinase β (IKKβ) complex. IKK β is the key kinase in the NF‐κB activation pathway. After inhibition, it can block the activation of NF‐κB. IKKβ is a key regulator of NF‐κB activation, also an early regulator of inflammation in all stages of the immune response. This study aimed to investigate the effect of IKKβ‐siRNA lentivirus vector treatment for hepatic fibrosis of rats. An IKKβ‐siRNA expression plasmid was constructed and injected in the tail vein of rats. Then, IKKβ‐siRNA distribution in the liver was observed by immunofluorescence, and the quantitative polymerase chain reaction was used to detect inflammation‐related and fibrosis‐related factors. IKKβ‐siRNA lentiviruses could be delivered to the liver and significantly decrease carbon tetrachloride‐induced hepatic fibrosis. Furthermore, serum transaminase levels significantly decreased, and inflammation‐related and fibrosis‐related factors decreased. IKKβ‐siRNA can be an effective method of anti‐fibrosis gene therapy for liver fibrosis.

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RNA interference targeting the platelet‐derived growth factor receptor β subunit ameliorates experimental hepatic fibrosis in rats

Cited by 39 publications

References 29 publications

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Silencing platelet-derived growth factor receptor-β enhances the radiosensitivity of C6 glioma cells in vitro and in vivo

Protective effect of RNA interference targeting Ikkβ on hepatic fibrosis in rats

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