Autophagy prevents irradiation injury and maintains stemness through decreasing ROS generation in mesenchymal stem cells.
Autophagy prevents irradiation injury and maintains stemness through decreasing ROS generation in mesenchymal stem cells.
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自噬通过减少间充质干细胞中ROS的产生来防止辐射损伤并保持干性
DOI：
10.1038/cddis.2013.338
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发表时间：
2013-10-10
影响因子：
9
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中科院分区：
文献类型：
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干细胞的特点是具有干性、自我更新和多能性。间充质干细胞（Mesenchymal stem cells, MSCs）是一种独特的成体干细胞，已被证明参与组织修复、免疫调节和肿瘤发生。辐照是导致干细胞功能障碍的一个众所周知的因素。然而，暴露于辐照下的人间充质干细胞的干细胞维持机制尚不清楚。我们证明了辐照可以诱导活性氧（ROS）积累，导致MSCs的DNA损伤和干性损伤。饥饿或雷帕霉素诱导的自噬可以减少ROS积累相关的DNA损伤，维持MSCs的干性。此外，抑制自噬导致ROS积累增加和DNA损伤，从而导致MSCs的干性丧失。我们的研究结果表明，自噬可能在保护MSCs的干性免受辐照损伤中起重要作用。
Stem cells were characterized by their stemness: self-renewal and pluripotency. Mesenchymal stem cells (MSCs) are a unique type of adult stem cells that have been proven to be involved in tissue repair, immunoloregulation and tumorigenesis. Irradiation is a well-known factor that leads to functional obstacle in stem cells. However, the mechanism of stemness maintenance in human MSCs exposed to irradiation remains unknown. We demonstrated that irradiation could induce reactive oxygen species (ROS) accumulation that resulted in DNA damage and stemness injury in MSCs. Autophagy induced by starvation or rapamycin can reduce ROS accumulation-associated DNA damage and maintain stemness in MSCs. Further, inhibition of autophagy leads to augment of ROS accumulation and DNA damage, which results in the loss of stemness in MSCs. Our results indicate that autophagy may have an important role in protecting stemness of MSCs from irradiation injury.