Wang Zhe, Li Hongqiu, Guo Ran, Wang Qiushi, Zhang Dianbao
Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Department of Orthopedics, Central Hospital of Shenyang Medical College, Shenyang 110024, China.
Sci Rep. 2016 Mar 11;6:23021. doi: 10.1038/srep23021.
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.
晚期糖基化终产物（AGEs）是诱导间充质干细胞凋亡的内源性炎症介质。一种潜在机制包括活性氧（ROS）生成增加。微小RNA-223（miR-223）参与多种细胞类型的细胞生长和凋亡调控。在此，我们检验了以下假设：抗氧化剂N-乙酰半胱氨酸（NAC）和抗坏血酸2-磷酸酯（AAP）通过微小RNA依赖性机制抑制人脂肪组织来源干细胞（ADSCs）中AGE诱导的凋亡。结果显示，AGE-HSA增强了ADSCs中的凋亡和半胱天冬酶-3活性。AGE-HSA还增加了ROS生成并上调了miR-223的表达。有趣的是，在用抗氧化剂NAC和AAP处理的ADSCs中发现ROS生成和凋亡减少，且miR-223上调。此外，miR-223模拟物阻断了抗氧化剂对AGE诱导的凋亡和ROS生成的抑制作用。敲低miR-223增强了抗氧化剂对AGE-HSA诱导的凋亡的保护作用。miR-223通过靶向成纤维细胞生长因子受体2发挥作用。这些结果表明，NAC和AAP可能通过下调miR-223抑制AGE-HSA诱导的ADSCs凋亡。
