Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling.
Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling.
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DOI：
10.1016/j.stem.2014.05.009
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发表时间：
2014-08-07
期刊：
影响因子：
23.9
通讯作者：
Gomperts, Brigitte N.
中科院分区：
文献类型：
--
作者：
Paul, Manash K.;Bisht, Bharti;Darmawan, Daphne O.;Chiou, Richard;Ha, Vi L.;Wallace, William D.;Chon, Andrew T.;Hegab, Ahmed E.;Grogan, Tristan;Elashoff, David A.;Alva-Ornelas, Jackelyn A.;Gomperts, Brigitte N.
呼吸道暴露于无数的环境和破坏性因素，如活性氧（ROS），它也具有调节干细胞功能的信号分子的生理作用。然而，在不同的干细胞群体中稳定和动态变化的ROS水平的功能意义，以及将ROS传感整合到关于干细胞稳态的决策中的下游机制，尚不清楚。在这里，我们在小鼠和人气道基底干细胞（ABSC）中发现，干细胞自我更新和增殖需要从低到中等ROS水平的细胞内通量。改变ROS水平激活Nrf2，Nrf2激活Notch途径以刺激ABSC自我更新以及清除细胞内ROS的抗氧化程序，使总体ROS水平恢复到低状态以维持稳态平衡。这种氧化还原介导的肺干细胞功能调节对干细胞生物学、肺损伤修复和癌症等疾病具有重要意义。
Airways are exposed to myriad environmental and damaging agents such as reactive oxygen species (ROS), which also have physiological roles as signaling molecules that regulate stem cell function. However, the functional significance of both steady and dynamically changing ROS levels in different stem cell populations, as well as downstream mechanisms that integrate ROS sensing into decisions regarding stem cell homeostasis, are unclear. Here, we show in mouse and human airway basal stem cells (ABSCs) that intracellular flux from low to moderate ROS levels is required for stem cell self-renewal and proliferation. Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal as well an antioxidant program that scavenges intracellular ROS, returning overall ROS levels to a low state to maintain homeostatic balance. This redox-mediated regulation of lung stem cell function has significant implications for stem cell biology, repair of lung injuries, and diseases such as cancer.
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影响因子：
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作者：
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DOI：
10.1165/rcmb.2013-0049oc
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