Department of Burns, The First People's Hospital of Zhengzhou, Zhengzhou, 450000, Henan, People's Republic of China.
School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.
J Neural Transm (Vienna). 2019 Dec;126(12):1589-1597. doi: 10.1007/s00702-019-02102-z. Epub 2019 Nov 9.
Microglia are the resident mononuclear immune cells of the central nervous system (CNS) and the activation of microglia contributes to the production of excessive neurotoxic factors. In particular, the overproduction of neurotoxic factors has critical effects on the development of brain injuries and neurodegenerative diseases. The human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have blossomed into an effective approach with great potential for the treatment of neurodegenerative diseases and gliomas. The present study aimed to investigate the mechanism behind the therapeutic effect of hBM-MSCs on the activation of microglia in vitro. Specifically, the hBM-MSCs significantly inhibited the proliferation of lipopolysaccharide-activated microglial cells (LPS)-activated microglial cells. Additionally, we investigated whether the adenosine-monophosphate-activated protein kinase signaling (AMPK) pathway was involved in this process. Our data demonstrated that hBM-MSCs significantly increased the phosphorylated AMPK in LPS-activated microglial cells. In addition, our study indicated the inhibitory effect of hBM-MSCs on the pro-inflammatory mediators and oxidative stress by the AMPK pathway in LPS-activated microglial cells. These results could shed light on the understanding of the molecular basis for the inhibition of hBM-MSCs on LPS-activated microglial cells and provide a molecular mechanism for the hBM-MSCs implication in brain injuries and neurodegenerative diseases.
小胶质细胞是中枢神经系统 (CNS) 的常驻单核免疫细胞,小胶质细胞的激活导致过度产生神经毒性因子。特别是,神经毒性因子的过度产生对脑损伤和神经退行性疾病的发展有至关重要的影响。人骨髓间充质干细胞 (hBM-MSCs) 已成为治疗神经退行性疾病和神经胶质瘤的一种有很大潜力的有效方法。本研究旨在探讨 hBM-MSCs 对体外小胶质细胞激活的治疗作用的机制。具体来说,hBM-MSCs 显著抑制脂多糖激活的小胶质细胞 (LPS-激活的小胶质细胞) 的增殖。此外,我们还研究了是否涉及腺苷一磷酸激活蛋白激酶信号通路 (AMPK)。我们的数据表明,hBM-MSCs 显著增加了 LPS 激活的小胶质细胞中磷酸化的 AMPK。此外,我们的研究表明,hBM-MSCs 通过 LPS 激活的小胶质细胞中的 AMPK 途径抑制促炎介质和氧化应激。这些结果可以为理解 hBM-MSCs 对 LPS 激活的小胶质细胞的抑制作用的分子基础提供信息,并为 hBM-MSCs 在脑损伤和神经退行性疾病中的作用提供分子机制。