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Anti‐senescence effects of DNA methyltransferase inhibitor RG108 in human bone marrow mesenchymal stromal cells
Author(s) -
Oh Youn Seo,
Jeong SinGu,
Cho GoangWon
Publication year - 2015
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1002/bab.1393
Subject(s) - mesenchymal stem cell , senescence , stromal cell , dna methylation , bone marrow , methyltransferase , ageing , dna methyltransferase , methylation , biology , cell , cancer research , microbiology and biotechnology , gene expression , immunology , gene , biochemistry , genetics
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.