tailieunhanh - Antisenescence activity of G9a inhibitor BIX01294 on human bone marrow mesenchymal stromal cells

Alterations in epigenomic patterns are associated with diverse physiological functions and pathological mechanisms causing aging-related diseases, such as degenerative disorders and cancers. | Turkish Journal of Biology Turk J Biol (2016) 40: 443-451 © TÜBİTAK doi: Research Article Antisenescence activity of G9a inhibitor BIX01294 on human bone marrow mesenchymal stromal cells 1,2 1,2 1,2, Min-Ji AHN , Sin-Gu JEONG , Goang-Won CHO * Department of Biology, College of Natural Science, Chosun University, Gwangju, Korea 2 Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, Korea 1 Received: Accepted/Published Online: Final Version: Abstract: Alterations in epigenomic patterns are associated with diverse physiological functions and pathological mechanisms causing aging-related diseases, such as degenerative disorders and cancers. We investigated the senescent effects of BIX01294, a G9a (histone methyltransferase) inhibitor, in human bone marrow mesenchymal stromal cells (hBM-MSCs). We determined the optimal dose and time of BIX01294 treatment in hBM-MSCs to be 1 µM and 12 h, respectively. Under these conditions, the expression of the antisenescent genes TERT, bFGF, VEGF, and Oct-4 increased, whereas the expression of the senescent factors p16, p21, and p53 decreased. The number of β-galactosidase-positive cells decreased significantly, and the rates of migration and cellular protection against oxidative damage increased in BIX01294-treated MSCs. These data indicate that an optimized dose of BIX01294 may improve the potency and senescence of stem cells, which may improve the efficacy of stem cell therapy. Key words: Antiaging, antisenescence, BIX01294, G9a inhibitor, histone methyltransferase, mesenchymal stromal cells 1. Introduction Stem cells are often expanded under in vitro culture conditions to obtain sufficient quantities of cells for cell therapy. However, the cellular protection (Nagai et al., 2007; Cho et al., 2010b) and differentiation (Pittenger et al., 1999; Jeong et al., 2013) .