title: Anti-senescence effects of DNA methyltransferase inhibitor RG108 in human bone marrow mesenchymal stromal cells.
abstract: Alteration of DNA methylation is highly associated with ageing and ageing-related diseases. Remedy of the altered methylation pattern may provide beneficial efficacy in these diseases. In this study, we used a DNA methyltransferase inhibitor, RG108, to investigate the senescence effects in human bone marrow mesenchymal stromal cells (hBM-MSCs). First, we determined the optimized dose and time of RG108 treatment in hBM-MSCs to be 5 µM for 48 H, respectively. Under these conditions, the anti-senescence genes TERT, bFGF, VEGF, and ANG were increased, whereas the senescence-related genes ATM, p21, and p53 were decreased. The number of β-galactosidase-positive cells was significantly decreased in RG108-treated MSCs, whereas the rates of MSC migration and cellular protection were increased. We have shown that RG108 significantly induces the expression of TERT by blocking methylation at the TERT promoter region. Thus, these data indicate that an optimized dose of RG108 may improve the cell migration, protection, cellular senescence, which may provide a better efficacy of these cells in stem cell therapy.
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju, Korea.|Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, Korea.
authors.forename: Youn Seo
authors.initials: YS
authors.lastname: Oh
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju, Korea.|Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, Korea.
authors.forename: Sin-Gu
authors.initials: SG
authors.lastname: Jeong
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju, Korea.|Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, Korea.
authors.forename: Goang-Won
authors.initials: GW
authors.lastname: Cho
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D019175:DNA Methylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010797:Phthalimides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010797:Phthalimides; C503639:RG108; D016222:Fibroblast Growth Factor 2; D014364:Tryptophan; D004248:DNA (Cytosine-5-)-Methyltransferases; C509186:TERT protein, human; D019098:Telomerase
keywords: DNA methyltransferase; DNMT inhibitor; RG108; anti-ageing; anti-senescence; mesenchymal stromal cells