The effects of the DNA methyltranfserases inhibitor 5-Azacitidine on ageing, oxidative stress and DNA methylation of adipose derived stem cells
Katarzyna Kornicka , Krzysztof Marycz , Monika Marędziak , Krzysztof A. Tomaszewski , Jakub Nicpoń
AbstractHuman adipose tissue is a great source of adult mesenchymal stem cells (MSCs) which are recognized from their ability to self-renew and differentiation into multiple lineages. MSCs have promised a vast therapeutic potential in treatment many diseases including tissue injury and immune disorders. However, their regenerative potential profoundly depends on patients' age. Age-related deterioration of MSC is associated with cellular senescence mainly caused by increased DNA methylation status, accumulation of oxidative stress factors and mitochondria dysfunction. We found that DNA methyltransferase (DNMT) inhibitor i.e. 5-Azacytidine (5-AZA) reversed the aged phenotype of MSCs. Proliferation rate of cells cultured with 5-AZA was increased while the accumulation of oxidative stress factors and DNA methylation status were decreased. Simultaneously the mRNA levels of TET proteins involved in demethylation process were elevated in those cells. Moreover, cells treated with 5-AZA displayed reduced reactive oxygen species (ROS) accumulation, ameliorated superoxide dismutase activity and increased BCL-2/BAX ratio in comparison to control group. Our results indicates that, treating MSCs with 5-AZA can be justified therapeutic intervention, that can slow-down and even reverse aged- related degenerative changes in those cells.
|Journal series||Journal of Cellular and Molecular Medicine, ISSN 1582-4934, [1582-1838], (A 35 pkt)|
|Publication size in sheets||0.7|
|Keywords in English||mesenchymal stem cells; ageing; methylation; oxidative stress; 5-Azacitidine|
|Internal identifier||62535; PX-58e5e9aad5de932aa11a8da8; PX-58e5f1ced5de932aa11a920f|
|License||Journal (articles only); published final; ; after publication|
|Score||= 35.0, 02-09-2020, ArticleFromJournal|
|Publication indicators||= 39; = 39; : 2017 = 1.104; : 2017 = 4.302 (2) - 2017=4.252 (5)|
|Citation count*||47 (2020-09-30)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.