| 引用本文： |
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马蓉洁,朱良,徐俊.Wnt/β-catenin信号通路调控人神经干细胞衰老过程的研究[J].同济大学学报（医学版）,2017,38(5):1-6. [点击复制]
- MA Rong-jie,ZHU Liang,XU Jun.Wnt/β-catenin signal pathway regulates senescence of human neural stem cells[J].同济大学学报（医学版）,2017,38(5):1-6. [点击复制]
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| 摘要: |
| 目的 探讨Wnt/β-catenin信号通路对人神经干细胞（neural stem cells, NSCs）衰老的调控作用。方法将人胚胎干细胞分化为NSCs，经MPTP（1-甲基-4-苯基-1，2，3，6-四氢吡啶）处理后，检测细胞的衰老表型和Wnt/β-catenin相关蛋白表达变化。分别应用AR-A014418、DKK1蛋白激活、抑制Wnt/β-catenin通路后，检测Wnt/β-catenin信号通路改变对细胞衰老表型的影响。检测各实验组和对照组中促炎因子CCL3、CXCL10、CXCL11、TNF-α的表达变化。结果经MPTP处理后，NSCs显示衰老表型，表现为SA-β-gal阳性细胞明显增多，胞内ROS水平明显升高、细胞增殖活性受到抑制（P<0.01）。同时，Wnt1、β-catenin蛋白表达降低，磷酸化GSK3β表达升高。AR-A014418激活了Wnt/β-catenin通路，缓解了细胞的衰老表型；DKK1蛋白抑制了Wnt/β-catenin通路，加重了细胞的衰老表型。Wnt/β-catenin通路能调控NSCs衰老过程中促炎因子的表达。结论Wnt/β-catenin信号通路能够调控MPTP诱导的NSCs衰老过程。 |
| 关键词: 神经干细胞 衰老 Wnt/β-catenin信号通路 促炎因子 |
| DOI：10.16118/j.1008-0392.2017.05.001 |
| 投稿时间：2017-06-12 |
| 基金项目:国家自然科学基金（31471029） |
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| Wnt/β-catenin signal pathway regulates senescence of human neural stem cells |
| MA Rong-jie,ZHU Liang,XU Jun |
| (Translational Medicine Center, East Hospital, Tongji University, Shanghai 200120, China) |
| Abstract: |
| Objective To investigate the effects of Wnt/β-catenin signal pathway on aging process of human neural stem cells. MethodsHuman neural stem cells were induced from human embryonic stem cells. After MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin) treatment, the senescent phenotypes were detected and the expression of genes in Wnt/β-catenin pathway were examined. AR-A014418 and DKK1 proteins were used to activate or inhibit Wnt/β-catenin pathway，respectively. The effects of Wnt/β-catenin pathway on cell aging phenotypes were studied, the expression of proinflammatory cytokines CCL3, CXCL10, CXCL11 and TNF-α were detected. ResultsMPTP induced significant senescent phenotypes in neural stem cells, such as elevated SA-β-gal staining and intracellular ROS levels, compromised proliferation (P<0.01). Meanwhile, the expression of Wnt1 and β-catenin was inhibited and p-GSK3β protein levels increased significantly during this process of aging. Stimulation of Wnt/β-catenin pathway with AR-A014418 alleviated the aging phenotypes. Inhibition of Wnt/β-catenin pathway with DKK1 proteins aggravated premature aging process. Wnt/β-catenin pathway regulated the expression of proinflammatory cytokines. ConclusionWnt/β-catenin signal pathway regulates the aging process of neural stem cells induced by MPTP treatment. |
| Key words: neural stem cells aging Wnt/β-catenin pathway proinflammatory cytokine |
