RNAa-Mediated Epigenetic Attenuation of The Cell Senescence via Locus Specific Induction of Endogenous SIRT1

2021 ◽  
Author(s):  
Neda Mokhberian ◽  
Kazem Sharifi ◽  
Ehsan Soleimaninejadian ◽  
Mohamad Eftekhary ◽  
Seyed Mahmoud Hashemi ◽  
...  
Keyword(s):  
Antisense Transcript ◽  
Human Mesenchymal Stem Cell ◽  
Specific Gene ◽  
Human Mscs ◽  
Natural Antisense Transcript ◽  
Molecular Alterations ◽  
Age Related ◽  
Proliferation And Differentiation ◽  
Specific Induction ◽  
Single Stranded Oligonucleotide

Abstract SIRT1, a known regulator of cellular senescence, is a therapeutic target for age related disorders and its upregulation is a strategy to improve the cell therapeutic potentials of human mesenchymal stem cell (MSCs). Knockdown of natural antisense transcripts via small activating RNAs (RNAa) is an emerging approach for safe and locus specific gene regulation. We have recently identified a natural antisense transcript at human SIRT1 locus (SIRT1-NAT), the expression of which shows a negative correlation with that of SIRT1. To test the hypothetic upregulation of SIRT1 via knockdown of SIRT1-NAT, in this study we designed a single stranded oligonucleotide (SIRT1-antagoNAT) against the antisense transcript, transfection of which efficiently knocked down the SIRT1-NAT and induced SIRT1 transcription in human MSCs. In addition, activation of SIRT1 transfection via knockdown of SIRT1-NAT in human MSCs enhanced their proliferation and differentiation potentials, reduced senescence associated β-galactosidase activity and reversed the senescence associated molecular alterations. Our findings introduce an RNAa mediated approach for epigenetic induction of endogenous SIRT1 and the consequent attenuation of senescence. Further studies should evaluate the therapeutic potentials of this approach against various age related disorders.

scholarly journals Natural Antisense Transcript PEBP1P3 Regulates the RNA Expression, DNA Methylation and Histone Modification of CD45 Gene

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 759
Author(s):  
Zhongjing Su ◽  
Guangyu Liu ◽  
Bin Zhang ◽  
Ze Lin ◽  
Dongyang Huang
Keyword(s):  
Dna Methylation ◽  
Alternative Splicing ◽  
Histone Modification ◽  
Antisense Rna ◽  
Noncoding Rna ◽  
Antisense Transcript ◽  
Natural Antisense Transcript ◽  
Regulation Of Expression ◽  
Splicing Isoforms ◽  
Intron 2

The leukocyte common antigen CD45 is a transmembrane phosphatase expressed on all nucleated hemopoietic cells, and the expression levels of its splicing isoforms are closely related to the development and function of lymphocytes. PEBP1P3 is a natural antisense transcript from the opposite strand of CD45 intron 2 and is predicted to be a noncoding RNA. The genotype-tissue expression and quantitative PCR data suggested that PEBP1P3 might be involved in the regulation of expression of CD45 splicing isoforms. To explore the regulatory mechanism of PEBP1P3 in CD45 expression, DNA methylation and histone modification were detected by bisulfate sequencing PCR and chromatin immunoprecipitation assays, respectively. The results showed that after the antisense RNA PEBP1P3 was knocked down by RNA interference, the DNA methylation of CD45 intron 2 was decreased and histone H3K9 and H3K36 trimethylation at the alternative splicing exons of CD45 DNA was increased. Knockdown of PEBP1P3 also increased the binding levels of chromatin conformation organizer CTCF at intron 2 and the alternative splicing exons of CD45. The present results indicate that the natural antisense RNA PEBP1P3 regulated the alternative splicing of CD45 RNA, and that might be correlated with the regulation of histone modification and DNA methylation.

scholarly journals Non-medical treatment for late age-related macular degeneration

2021 ◽  
Vol 21 (4) ◽  
pp. 215-219
Author(s):  
A.K. Drakon ◽  
◽  
A.G. Kurguzova ◽  
V.M. Sheludchenko ◽  
N.B. Korchazhkina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Medical Treatment ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Target Cells ◽  
Specific Gene ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 55 in developed countries. Moreover, the number of these patients will increase growth as life expectancy increases. It is estimated that late AMD accounts for half of blindness and low vision cases in European countries. A myriad of studies is currently underway to discover cutting-edge, effective therapeutic modalities. Gene therapy is a novel alternative to regular intravitreal injections of anti-VEGF agents for late wet AMD. This technique’s heart is a specific gene delivery to target cells to generate natural VEGF inhibitors. Gene therapy affecting the complement system to deactivate its end product, the membrane attack complex, is reasonable in late atrophic AMD. Studies on stem cell therapy for late atrophic AMD undergo as well. It was demonstrated that retinal pigment epithelium (RPE) cells derived from human embryonic stem cells or induced pluripotent stem cells express typical RPE markers that can phagocytize photoreceptor segments. Electrical stimulation and magnet therapy are already introduced into clinical practice to rehabilitate patients with late AMD. Magnetic and electrical fields improve impulse transmitting, activate intracellular and tissue regeneration of the retina. Recent findings are promising but require further in-depth studies. Keywords: age-related macular degeneration, retinal scar, gene therapy, stem cells, physiotherapy, rehabilitative medicine. For citation: Drakon A.K., Kurguzova A.G., Sheludchenko V.M., Korchazhkina N.B. Non-medical treatment for late age-related macular degeneration. Russian Journal of Clinical Ophthalmology. 2021;21(4):215–219 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-215-219.

scholarly journals Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations Under Maternal High-Fat Diet Intake: Multigenerational Epigenetic Inheritance.

2020 ◽  
Author(s):  
Vanesa Izquierdo ◽  
Verónica Palomera-Ávalos ◽  
Mercè Pallàs ◽  
Christian Griñán-Ferré
Keyword(s):  
Gene Expression ◽  
Cognitive Decline ◽  
High Fat Diet ◽  
Epigenetic Inheritance ◽  
Adult Offspring ◽  
High Fat ◽  
Molecular Alterations ◽  
Protein Levels ◽  
Age Related ◽  
Inflammatory Profile

Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.

Long noncoding RNA FGFR3-AS1 promotes osteosarcoma growth through regulating its natural antisense transcript FGFR3

2016 ◽  
Vol 43 (5) ◽  
pp. 427-436 ◽  
Author(s):  
Jiabing Sun ◽  
Xuming Wang ◽  
Chunjiang Fu ◽  
Xiaoyu Wang ◽  
Jilong Zou ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Antisense Transcript ◽  
Natural Antisense Transcript

Effect of the Pore Structure of an Apatite-Fiber Scaffold on the Differentiation of P19.CL6 Cells into Cardiomyocytes

2018 ◽  
Vol 782 ◽  
pp. 116-123
Author(s):  
Yuzuha Ichikawa ◽  
Kei Yasuda ◽  
Masahiro Takahara ◽  
Mamoru Aizawa ◽  
Nobuyuki Kanzawa
Keyword(s):  
Troponin T ◽  
Specific Gene ◽  
Porous Hydroxyapatite ◽  
Spherical Carbon ◽  
Functional Maturation ◽  
Biomedical Device ◽  
Hydroxyapatite Ceramics ◽  
Proliferation And Differentiation ◽  
Device Applications ◽  
Radial Flow Bioreactor

We previously reported that P19.CL6 cells can be cultured in porous hydroxyapatite ceramics prepared by firing green compacts consisting of apatite fibers and spherical carbon beads (150 μm in diameter). Cells cultured for 20 days in an apatite-fiber scaffold (AFS) proliferated and differentiated into cells expressing troponin T, a cardiomyocyte-specific gene, but the expression level was insufficient to support the functional maturation of cells required for biomedical device applications. In this study, we aimed to optimize the internal AFS environment for cardiomyocytes by mixing two sizes (150-and 20-μm) of carbon beads. P19.CL6 cells were cultured in AFS materials comprising different carbon ratios in the presence of alpha-MEM with (AFS+) or without (AFS-) dimethyl sulfoxide (DMSO), and cell growth and gene expression were assessed. We found that AFS(50, 1:1 ratio) is the most suitable scaffold for the proliferation and differentiation of P19.CL6 cells and the addition of DMSO to the culture medium is necessary for differentiation into cardiomyocytes. We also assessed the culture of P19.CL6 cells in AFS in a radial-flow bioreactor for several days.

P4-264: A GENE THERAPY APPROACH FOR REDUCTION OF TAU BY TAU LONG NON-CODING RNA GENE (MAPT-AS1 ) NATURAL ANTISENSE TRANSCRIPT

2006 ◽  
Vol 14 (7S_Part_29) ◽  
pp. P1547-P1548
Author(s):  
Rohan de Silva ◽  
Justyna Zareba-Paslawska ◽  
Filipa Almeida ◽  
Per Svenningsson ◽  
Tom Warner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Antisense Transcript ◽  
Natural Antisense Transcript ◽  
Therapy Approach ◽  
Gene Therapy Approach ◽  
Non Coding Rna ◽  
Long Non Coding Rna
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