Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca(2+) -ATPase Isoform1.

Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca(2+) -ATPase Isoform1.
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DOI:
10.3389/fcell.2020.586541
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发表时间:
2020
影响因子:
5.5
通讯作者:
Hu Z
Hu Z
中科院分区:
生物学2区
文献类型:
--
作者:
He J;Liu J;Huang Y;Zhuo Y;Chen W;Duan D;Tang X;Lu M;Hu Z

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嗅粘膜间充质干细胞(OM-MSCs)在中枢神经系统疾病中表现出其有效性,并为缺血性脑卒中的治疗提供了一个有吸引力的候选者。已有证据表明,高尔基体(GA)分泌途径Ca 2 +-ATP酶亚型1(SPCA 1)是缺血性脑卒中潜在的治疗靶点。本研究旨在探讨OM-MSCs对脑缺血再灌注损伤的神经保护机制及其对SPCA 1表达和功能的影响。在体内外实验的基础上,我们发现OM-MSCs能减轻缺血性脑卒中模型中的细胞凋亡和氧化应激,减少脑梗死体积,改善大鼠的神经功能缺损。OM-MSCs还上调SPCA 1表达,减轻神经元内Ca 2+超载,减少GA的水肿和溶解。此外,我们发现,SPCA 1消耗在氧和葡萄糖剥夺/复氧(OGD/R)处理的N2 a细胞减轻了OM-MSC的保护作用。总之,OM-MSCs可能通过调节SPCA 1和减少神经元中GA的水肿和溶解而对缺血性卒中发挥神经保护作用。
Olfactory mucosa mesenchymal stem cells (OM-MSCs) have exhibited their effectiveness in central nervous system diseases and provided an appealing candidate for the treatment of ischemic stroke. Previous evidence have shown that Golgi apparatus (GA) secretory pathway Ca2+-ATPase isoform1 (SPCA1) was a potential therapeutic target for ischemic stroke. In this study, we explored the neuroprotective mechanism of OM-MSCs and its effect on the expression and function of SPCA1 during cerebral ischemia/reperfusion. Based on in vitro and in vivo experiments, we discovered that OM-MSCs attenuated apoptosis and oxidative stress in ischemic stroke models, reduced the cerebral infarction volume, and improved the neurologic deficits of rats. OM-MSCs also upregulated SPCA1 expression and alleviated Ca2+ overload and decreased the edema and dissolution of the GA in neurons. Moreover, we discovered that SPCA1 depletion in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated N2a cells mitigated the protective effects of OM-MSCs. Altogether, OM-MSCs exerted neuroprotective effects in ischemic stroke probably via modulating SPCA1 and reducing the edema and dissolution of the GA in neurons.
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