Metformin promotes neuronal differentiation and neurite outgrowth through AMPK activation in human bone marrow-mesenchymal stem cells
Metformin promotes neuronal differentiation and neurite outgrowth through AMPK activation in human bone marrow-mesenchymal stem cells
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DOI：
10.1002/bab.1584
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发表时间：
2017-11-01
影响因子：
2.8
通讯作者：
Cho, Goang-Won
中科院分区：
文献类型：
--
作者：
Ahn, Min-Ji;Cho, Goang-Won
二甲双胍是一种AMPK激活剂，在葡萄糖能量代谢和细胞保护中发挥作用。它被广泛用于治疗多种疾病，包括2型糖尿病、心血管疾病、癌症和代谢性疾病。在本研究中，我们研究了在人骨髓间充质干细胞(HBM-MSCs)向神经元分化的过程中，二甲双胍处理后AMPK的激活是否促进了神经突起的生长。二甲双胍处理的MSCs(Met-MSCs向Met-diMSCs)在神经元诱导液中的分化导致分化的细胞数量增加，并呈浓度依赖关系。经神经诱导培养液诱导后3h分化率最高。诱导后3h，Met-diMSCs的轴突长度明显高于未加二甲双胍的对照细胞(DiMSCs)。免疫印迹结果显示，与diMSCs相比，Met-diMSCs中神经元特异性标记基因的表达显著增加，而树突特异性标记MAP-2和Tuj-1的表达显著增加。用AMPK抑制剂化合物C处理后，这种作用被消除，定量聚合酶链式反应、免疫印迹和免疫细胞化学染色证明了这一点。因此，二甲双胍通过激活AMPK促进HBM-MSCs的神经元分化和轴突生长。(C)2017年国际生物化学和分子生物学联合会。
Metformin is an AMP-activated kinase (AMPK) activator that plays a role in glucose energy metabolism and cell protection. It is widely used to treat several diseases, including type 2 diabetes, cardiovascular diseases, cancer, and metabolic diseases. In this study, we investigated whether AMPK activation upon treatment with metformin may promote neurite outgrowth during the progression of neuronal differentiation in human bone marrow-mesenchymal stem cells (hBM-MSCs). Differentiation of metformin-treated MSCs (Met-MSCs to Met-diMSCs) in the neuronal induction media resulted in an increase in the number of differentiated cells in a metformin concentration dependent manner. The differentiation rate reached its maximum at 3 H after the initial treatment with neuronal induction media. At 3 H of induction, the neurite length increased significantly in Met-diMSCs as compared with control cells without metformin treatment (diMSCs). diMSCs showed a significant increase in the expression of neuronal-specific marker genes; however, the expression of dendrite-specific markers MAP-2 and Tuj-1 was significantly increased in Met-diMSCs as compared to diMSCs, as confirmed by immunoblotting. This effect was abolished upon treatment with the AMPK inhibitor, compound C, as evident by quantitative PCR, immunoblotting, and immunocytochemical staining. Thus, metformin treatment promotes neuronal differentiation and neurite outgrowth in hBM-MSCs through AMPK activation. (C) 2017 International Union of Biochemistry and Molecular Biology, Inc.