Transfected synthetic DNA Enzyme Gene specifically inhibits Egr-1 gene expression and reduces Neointimal Hyperplasia following balloon injury in rats

Gui-nan, Liu; Wu, Yan

doi:10.1016/j.ijcard.2007.11.066

Cited by 17 publications

(11 citation statements)

References 12 publications

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“…Therefore, the shear rate of the shear product DRz dissociation process is relatively small [45, 46]. The RNA of the DNA-RNA hybrid molecules can be degraded by the RNA enzyme H. Hence, the DNA enzyme can not only directly kill the target RNA such as Rz, but also cause the hydrolysis of the RNA enzyme H to target RNAs, such as ASODN [47, 48]. …”

Section: Discussionmentioning

confidence: 99%

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Wang

Cheng

et al. 2013

BioMed Research International

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The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz) as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft.

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Section: Discussionmentioning

confidence: 99%

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Wang

Cheng

et al. 2013

BioMed Research International

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“…These enzyme mimics have been developed as inhibitory agents for a myriad of diseases and their potential has been recognized in the past decade. For instance, a DNAzyme against the zinc finger transcription factor Egr-1 inhibited restenosis in balloon-injured rat carotid arteries,31 whereas DZ1133 was developed to target the conserved genomic RNA sequence of the RSV nucleocapsid protein and inhibit respiratory syncytial viral infection;32 recently, the anti-MMP9 DNAzyme AM9D was shown to reduce breast tumor growth in a MMTV-PyMT mouse model of breast cancer 33. DNAzymes have also been developed for use in bioanalytical in vitro applications, such as the detection of specific DNA sequences via peroxidase-like colorimetric/chemiluminescent assays, determination of telomerase or methyltransferase activity, determination of metal cations (Ag + , K + , Hg 2+ , Pb 2+ , or Cu 2+ ), and amplified detection of small molecules (eg, adenosine, cocaine, or adenosine monophosphate) and proteins (eg, lysozyme or thrombin) 34…”

Section: Discussionmentioning

confidence: 99%

Anti-insulin-like growth factor-IIP3 DNAzymes inhibit cell proliferation and induce caspase-dependent apoptosis in human hepatocarcinoma cell lines

Zhang¹,

Drummen²,

Luo³

2013

DDDT

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BackgroundInsulin-like growth factor II (IGF-II) is a fetal growth protein and an important proangiogenic factor controlled by four promoters (P), of which P2–P4 are inactive in the adult liver. Reactivation and dysregulation of IGF-IIP3 in particular is associated with the attenuation of apoptosis and increased proliferation in a number of liver cancer cell types. Its involvement in experimental liver carcinogenesis makes it a potential target for cancer gene therapy. We designed two IGF-IIP3 specific DNAzymes (DRz1 and DRz2) that target IGF-IIP3 messenger RNA (mRNA) with the aim of reducing IGF-II expression through promoter 3.MethodsIGF-IIP3 mRNA and protein expression levels were assessed using real-time polymerase chain reaction and gel electrophoresis/western blotting after transfection with Lipofectamine® in SMMC-7721, Huh7, and HepG2 cell lines. Cell proliferation was determined via MTT assay; apoptosis was evaluated by fluorescence microscopy and with flow cytometry; procaspase-3 and -9 expression were detected via western blotting; and caspase activity was assayed colorimetrically. Standard procedures were used to calculate means and standard deviations, and P-values below 0.05 were considered to indicate significant differences.ResultsDRzs were transfected into hepatocellular carcinoma cells and the results showed that DRz1, in particular, could decrease the expression of IGF-IIP3 by nearly 50%. Furthermore, DRz1 significantly inhibited cell proliferation and induced apoptosis. In addition, the down-regulation of IGF-IIP3 expression was associated with increased caspase-3 and -9 activity in SMMC-7721 cells after 24 hours of transfection. In all experiments, the efficacy of DRz2 to influence IGF-IIP3 levels and associated effects remained second to DRz1.ConclusionOverall, these results suggest that DRz1-based targeting of IGF-IIP3 mRNA might have antitumorigenic activity and may potentially provide the basis for a novel therapeutic intervention in liver cancer treatment, although further development is required.

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“…In fact, microarray studies suggest that EGR-1 participates in the regulation of at least thirty genes at the transcriptional level, thereby affecting cell growth, proliferation, differentiation and apoptosis (Fu et al 2003). Our earlier study indicates that a synthetic DNA enzyme target EGR-1 can improve vascular endothelial function and inhibit neointimal hyperplasia via upregulation of nitric oxide synthase (NOS) and down regulation of transforming growth factor beta (TGF-β) (Liu et al 2008). Therefore, EGR-1 is a promising target in the prevention and cure of AS and postangioplasty RS.…”

Section: Discussionmentioning

confidence: 99%

“…Under 10% chloral hydrate anesthesia, a Baxter 2F balloon catheter was introduced through the left external carotid artery and advanced into the aorta. The balloon was inflated with 200 μl normal sodium and was moved back to the carotid bifurcation three times (Liu et al 2008). Simultaneously, the transfection groups were perfused with a 200 μl mixture containing 500 μg ODNs, 30 μl FuGene6 (Cat.…”

Section: Transfection Of Odns Into Carotid Artery and Primary Culturementioning

confidence: 99%

EGR-1 decoy ODNs inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of balloon-injured arteries in rat

Han

Gui-nan

2010

Life Sciences

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Transfected synthetic DNA Enzyme Gene specifically inhibits Egr-1 gene expression and reduces Neointimal Hyperplasia following balloon injury in rats

Cited by 17 publications

References 12 publications

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Anti-insulin-like growth factor-IIP3 DNAzymes inhibit cell proliferation and induce caspase-dependent apoptosis in human hepatocarcinoma cell lines

EGR-1 decoy ODNs inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of balloon-injured arteries in rat

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