Wnt/β-catenin信号通路调控人神经干细胞衰老过程的研究  

Wnt/β-catenin signal pathway regulates senescence of human neural stem cells

作　　者：马蓉洁 朱良 徐俊[1] MA Rong-jie;ZHU Liang;XU Jun(Translational Medicine Center, East Hospital, Tongji University, Shanghai 200120, China)

机构地区：[1]同济大学附属东方医院干细胞工程转化医学中心,上海200120

出　　处：《同济大学学报（医学版）》2017年第5期1-6,共6页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金(31471029)

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。ObjectiveTo investigate the effects of Wnt/βcatenin signal pathway on aging process of human neural stem cells.MethodsHuman neural stem cells were induced from human embryonic stem cells.After MPTP(1methyl4phenyl1,2,3,6tetrahydropyridin)treatment,the senescent phenotypes were detected and the expression of genes in Wnt/βcatenin pathway were examined.AR A014418and DKK1proteins were used to activate or inhibit Wnt/βcatenin pathway,respectively.The effects of Wnt/βcatenin pathway on cell aging phenotypes were studied,the expression of proinflammatory cytokines CCL3,CXCL10,CXCL11and TNFαwere detected.ResultsMPTP induced significant senescent phenotypes in neural stem cells,such as elevated SAβgal staining and intracellular ROS levels,compromised proliferation(P<001).Meanwhile,the expression of Wnt1andβcatenin was inhibited and p GSK3βprotein levels increased significantly during this process of aging.Stimulation of Wnt/βcatenin pathway with AR A014418alleviated the aging phenotypes.Inhibition of Wnt/βcatenin pathway with DKK1proteins aggravated premature aging process.Wnt/βcatenin pathway regulated the expression of proinflammatory cytokines.ConclusionWnt/βcatenin signal pathway regulates the aging process of neural stem cells induced by MPTP treatment.

关 键 词：神经干细胞 衰老 Wnt/p-catenin信号通路 促炎因子 

分 类 号：R741[医药卫生—神经病学与精神病学]