Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production

被引:131
作者
Zhang, Da-yong [1 ]
Pan, Yu [1 ]
Zhang, Chong [1 ]
Yan, Bing-xi [1 ]
Yu, Shan-shan [1 ]
Wu, Dong-ling [1 ]
Shi, Meng-meng [1 ]
Shi, Kai [1 ]
Cai, Xin-xiao [1 ]
Zhou, Shuang-shuang [1 ]
Wang, Jun-bo [1 ]
Pan, Jian-ping [1 ]
Zhang, Li-huang [1 ]
机构
[1] Zhejiang Univ City Coll, Dept Basic Med, Sch Med & Life Sci, 51 Huzhou St, Hangzhou 310015, Zhejiang, Peoples R China
关键词
Mesenchymal stem cells (MSCs); Aging; Wnt/beta-catenin signaling; ROS; OXIDATIVE DNA-DAMAGE; CELLULAR SENESCENCE; WNT; PATHWAY; DIFFERENTIATION; ACTIVATION; MECHANISMS; DISEASE; CANCER; P53;
D O I
10.1007/s11010-012-1498-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recent studies have demonstrated that the Wnt/beta-catenin signaling plays an important role in stem cell aging. However, the mechanisms of cell senescence induced by Wnt/beta-catenin signaling are still poorly understood. Our preliminary study has indicated that activated Wnt/beta-catenin signaling can induce MSC aging. In this study, we reported that the Wnt/beta-catenin signaling was a potent activator of reactive oxygen species (ROS) generation in MSCs. After scavenging ROS with N-acetylcysteine, Wnt/beta-catenin signaling-induced MSC aging was significantly attenuated and the DNA damage and the expression of p16(INK4A), p53, and p21 were reduced in MSCs. These results indicated that the Wnt/beta-catenin signaling could induce MSC aging through promoting the intracellular production of ROS, and ROS may be the main mediators of MSC aging induced by excessive activation of Wnt/beta-catenin signaling.
引用
收藏
页码:13 / 20
页数:8
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