Abstract
Advanced glycosylation end products (AGEs) are endogenous inflammatory mediators that induce apoptosis of mesenchymal stem cells. A potential mechanism includes increased generation of reactive oxygen species (ROS). MicroRNA-223 (miR-223) is implicated in the regulation of cell growth and apoptosis in several cell types. Here, we tested the hypothesis that antioxidants N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) inhibit AGE-induced apoptosis via a microRNA-dependent mechanism in human adipose tissue-derived stem cells (ADSCs). Results showed that AGE-HSA enhanced apoptosis and caspase-3 activity in ADSCs. AGE-HSA also increased ROS generation and upregulated the expression of miR-223. Interestingly, reductions in ROS generation and apoptosis, and upregulation of miR-223 were found in ADSCs treated with antioxidants NAC and AAP. Furthermore, miR-223 mimics blocked antioxidant inhibition of AGE-induced apoptosis and ROS generation. Knockdown of miR-223 amplified the protective effects of antioxidants on apoptosis induced by AGE-HSA. miR-223 acted by targeting fibroblast growth factor receptor 2. These results indicate that NAC and AAP suppress AGE-HSA-induced apoptosis of ADSCs, possibly through downregulation of miR-223.