Autophagy induces G0/G1 arrest and apoptosis in menstrual blood-derived endometrial stem cells via GSK3-β/β-catenin pathway.
Autophagy induces G0/G1 arrest and apoptosis in menstrual blood-derived endometrial stem cells via GSK3-β/β-catenin pathway.
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自噬通过 GSK3-β/β-连环蛋白途径诱导经血来源的子宫内膜干细胞 G0/G1 停滞和凋亡
DOI：
10.1186/s13287-018-1073-0
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发表时间：
2018-11-28
影响因子：
7.5
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Du J;Zhu X;Guo R;Xu Z;Cheng FF;Liu Q;Yang F;Guan L;Liu Y;Lin J
背景/目的子宫内膜血液来源的子宫内膜干细胞（MenSC）成为再生医学和免疫治疗中基于细胞的治疗的理想来源。然而，主要的障碍是组织中的低存活率和有限的扩增数量。自噬是一种细胞内的代谢自降解过程，在正常细胞分裂和存活中起着重要作用，本研究旨在探讨自噬与MenSC在体内外存活的相关机制。在体外，将MenSC暴露于雷帕霉素和Earle平衡盐溶液（EBSS）。碘化丙啶（propidium iodide，PI）染色检测MenSC免疫表型细胞周期分布，Annexin V/PI染色检测细胞凋亡，MTT法检测细胞增殖能力。我们还通过蛋白质印迹分析评估了与细胞周期和Gsk 3 β信号通路相关的基因的表达。我们通过短发夹RNA（shRNA）抑制Atg 5和Gsk 3 β的表达并进行了实验。此外，标记的MenSC进行观察和计数后，通过尾静脉移植到小鼠体内显微镜下。结果在体外，雷帕霉素和饥饿诱导MenSC自噬。过度活跃的自噬显著诱导MenSC的G 0/G1期阻滞，并轻微促进MenSC的凋亡。同时，自噬可刺激MenSC中p-GSK 3 β的表达。此外，敲低GSK 3 β可以通过shRNA和CHIR 99021加速MenSC的增殖。结论自噬通过GSK 3 β/β-catenin途径诱导MenSCs发生G 0/G1期阻滞和凋亡。抑制自噬或降低GSK 3 β水平可以提高体内存活率，从而在MenSC治疗中发挥作用。
Background/aimsMenstrual blood-derived endometrial stem cells (MenSCs) emerge as an ideal source for cell-based treatment in regenerative medicine and immunotherapy. However, the major obstacle is the low survival rate in tissues and the limited expansion number. Autophagy is an intracellular metabolic self-degradative process which plays important roles in normal cellular division and survival, and the present study aimed to explore the related mechanisms between autophagy and survival of MenSCs in vitro and in vivo.MethodsThe MenSCs were obtained from menstrual blood procured from healthy female donors. In vitro, MenSCs were exposed to rapamycin and Earle’s balanced salts solution (EBSS). We evaluated the MenSCs immunophenotypic cell cycle distribution by propidium iodide (PI) staining and cell apoptosis by Annexin V/PI staining as well as their proliferative potential by the MTT assay. We also assessed the expression of genes associated with the cell cycle and Gsk3β signaling pathway by western blot analysis. We depressed Atg5 and Gsk3β expression by short hairpin RNA (shRNA) and undertook the experiments. Moreover, the labeled MenSCs were observed and counted with DiI after transplantation into the mice via the tail vein by microscopy in vivo.ResultsIn vitro, rapamycin and starvation induced autophagy of MenSCs. Hyperactive autophagy significantly induced G0/G1 arrest and slightly promoted apoptosis of MenSCs. Meanwhile, autophagy could stimulate p-GSK3β expression in MenSCs. Further, knockdown GSK3β can accelerate the proliferation of MenSCs by shRNA and CHIR99021. Moreover, the shGSK3β MenSCs showed strong proliferative activity in vitro and in vivo.ConclusionsOur results indicate that autophagy induced G0/G1 arrest and apoptosis of MenSCs via GSK3β/β-catenin pathway. Inhibiting autophagy or reduced GSK3β levels may improve survival rate in vivo, thus playing roles in MenSCs therapy.
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影响因子：
7.4
作者：
Meng, Xiaolong;Ichim, Thomas E.;Zhong, Jie;Rogers, Andrea;Yin, Zhenglian;Jackson, James;Wang, Hao;Ge, Wei;Bogin, Vladimir;Chan, Kyle W.;Thebaud, Bernard;Riordan, Neil H.
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影响因子：
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作者：
Dang S;Yu ZM;Zhang CY;Zheng J;Li KL;Wu Y;Qian LL;Yang ZY;Li XR;Zhang Y;Wang RX
通讯作者：
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影响因子：
21.3
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影响因子：
44.1
作者：
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通讯作者：
Oh, Sangtaek
DOI：
10.1126/science.1236566
发表时间：
2013-07-26
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Kang SA;Pacold ME;Cervantes CL;Lim D;Lou HJ;Ottina K;Gray NS;Turk BE;Yaffe MB;Sabatini DM
通讯作者：
Sabatini DM