期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 233, 期 10, 页码 7004-7015出版社
WILEY
DOI: 10.1002/jcp.26623
关键词
mesenchymal stem cells; myocardial infarction; Nox2; oxidant stress; ROS
资金
- Program for New Century Excellent Talents in Heilongjiang Provincial University [1252-NCET-013]
- National Natural Science Fund of China [81170096, 81573434]
An increase in reactive oxygen species (ROS) plays a key role in aging and apoptosis in mesenchymal stem cells derived from bone marrow (BMSCs). NADPH oxidase Nox2 serves as an important source of intracellular ROS formation. This study is designed to determine if blocking Nox2 enhances anti-apoptotic and anti-aging ability of BMSCs to oxidant stress, and thus improves therapeutic efficacy in myocardial infarction (MI). Nox2 inhibitor (Acetovanillone) and Nox2 siRNA were used to block Nox2 in BMSCs, and the cell viability, apoptosis, senescence and survival of BMSCs were determined by CCK-8, Edu staining, TUNEL staining, -galactosidase (-gal) assay and DAPI labeling. Here we found that both Nox2 inhibitor and Nox2 knockdown remarkably countered the decrease of viability, and the increase of aging and apoptosis of BMSCs by H2O2. Whereas, Nox2 overexpression exacerbated the viability reduction, senescence and apoptosis of BMSCs. The ROS accumulation in BMSCs was also suppressed by Nox2 blocking. Further study uncovered that Nox2 inhibitor caused the downregulation of p-p53, p21, p-FoxO1 and Bax, and the upregulation of anti-apoptotic protein Bcl-2. In vivo, Nox2 knockdown in grafted BMSCs led to the improvement of EF and FS in infarcted myocardium than BMSCs without Nox2 knockdown. Consistently, more retention and survival of BMSCs were found after Nox2 knockdown. Taken together, Nox2 inhibition enhances anti-aging and anti-apoptotic ability of BMSCs, and thus promotes survival and retention of BMSCs, which provides a new strategy for improving BMSCs-based therapy.
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