Nox2 and Nox4 Regulate Self-Renewal of Murine Induced-Pluripotent Stem Cells
Nox2 and Nox4 Regulate Self-Renewal of Murine Induced-Pluripotent Stem Cells
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Nox2 和 Nox4 调节小鼠诱导多能干细胞的自我更新
DOI：
10.1002/iub.1574
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发表时间：
2016-12-01
期刊：
影响因子：
4.6
通讯作者：
Meng, Dan
中科院分区：
文献类型：
--
作者：
Kang, Xueling;Wei, Xiangxiang;Meng, Dan
活性氧（ROS）和氧化还原稳态在维持干细胞多能性和干细胞自我更新中具有关键作用;然而，ROS调节干细胞自我更新的机制尚未得到彻底研究。在这里，我们评估了由NADPH氧化酶2（Nox 2）和NADPH氧化酶4（Nox 4）产生的ROS在小鼠诱导多能干细胞（miPSC）的自我更新和干细胞性中的作用。靶向沉默Nox 2或Nox 4可降低NADPH氧化酶活性和细胞内ROS水平，以及碱性磷酸酶活性、miPSC总数、胰岛素样生长因子-1（IGF-1）、IGF-1受体的表达和细胞外信号调节激酶（ERK）1/2的磷酸化。Nox 2/Nox 4过表达或低无毒浓度的H2 O2增加了miPSC中的细胞增殖。此外，干性基因Sox 2和Oct 4的表达在Nox 2/Nox 4缺陷的miPSC中较低，而在Nox 2/Nox 4过表达的miPSC中高于具有正常Nox 2/Nox 4表达水平的miPSC。总的来说，这些结果表明，Nox 2和Nox 4衍生的ROS有助于干细胞多能性维持和自我更新。(C)2016 IUBMB Life，68（12）：963-970，2016
Reactive oxygen species (ROS) and redox homeostasis have a pivotal role in the maintenance of stem cell pluripotency and in stem cell self-renewal; however, the mechanisms by which ROS regulate the self-renewal of stem cells have not been thoroughly studied. Here, we evaluated the role of the ROS produced by NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4) in the self-renewal and stemness of murine induced-pluripotent stem cells (miPSCs). Targeted silencing of Nox2 or Nox4 reduced both NADPH oxidase activity and intracellular ROS levels, as well as alkaline phosphatase activity, the total number of miPSCs, the expression of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and the phosphorylation of extracellular signal regulated kinase (ERK) 1/2. Nox2/Nox4 overexpression or low, nontoxic concentration of H2O2 increased cell proliferation in miPSCs. Furthermore, expression of the stemness genes Sox2 and Oct4 was lower in Nox2/Nox4-deficient miPSCs, and higher in Nox2/Nox4-overexpressing miPSCs, than in miPSCs with normal levels of Nox2/Nox4 expression. Collectively, these results suggest that Nox2- and Nox4-derived ROS contribute to stem cell pluripotency maintenance and self-renewal. (C) 2016 IUBMB Life, 68(12): 963-970, 2016