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Superoxide dismutase 3 protects mesenchymal stem cell through enhanced autophagy and regulation of FoxO3a trafficking
1Laboratory of Dermato-immunology, The Catholic University of Korea
Therapeutic implications of mesenchymal stem cells (MSCs) are limited due to early death within first few days of transplantation. To improve the efficacy of cell-based therapy, it is therefore, necessary to manipulate MSCs that could resist various stresses imposed by the microenvironment. Moreover, the role of superoxide dismutase 3 (SOD3) in regulating the survival under different stress conditions remain elusive. In this study, we overexpressed SOD3 in MSCs (SOD3-MSCs) and evaluated its effect under serum starvation condition. Nutritional limitation can decrease the survival rate of transplanted MSCs and thus can reduce their efficacy during therapy. Interestingly, we found that SOD3-MSCs exhibited reduced reactive oxygen species level and greater survival than the normal MSCs under serum-deprived condition. In addition, overexpression of SOD3 attenuated starvation-induced apoptosis with increased autophagy in MSCs. Moreover, we have demonstrated that SOD3 protects MSCs against serum-deprived insults via modulation of AMP-activated protein kinase/sirtulin 1, extracellular signal-regulated kinase activation, and promoted Forkhead box O3a trafficking to the nucleus. Taken together, these results demonstrated that SOD3 promotes MSCs survival and add further evidence to the concept that SOD3-MSCs may be potential therapeutic agent compared to normal MSCs for various diseases involving oxidative stress and compromised MSCs survival during therapy.
Abstract, Accepted Manuscript(in press) [Submitted on April 11, 2018, Accepted on May 24, 2018]
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