Olfactory Mucosa Mesenchymal Stem Cells Ameliorate Cerebral Ischemic/Reperfusion Injury Through Modulation of UBIAD1 Expression.
Olfactory Mucosa Mesenchymal Stem Cells Ameliorate Cerebral Ischemic/Reperfusion Injury Through Modulation of UBIAD1 Expression.
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嗅黏膜间充质干细胞通过调节UBIAD1的表达改善脑缺血再灌注损伤
DOI：
10.3389/fncel.2020.580206
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发表时间：
2020
影响因子：
5.3
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Liu J;Huang Y;He J;Zhuo Y;Chen W;Ge L;Duan D;Lu M;Hu Z
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）在脑缺血/再灌注（injury/reperfusion，I/R）中具有良好的神经保护作用。嗅粘膜间充质干细胞（Olfactory mucosa MSCs，OM-MSCs）是一种来源于鼻腔的新型间充质干细胞，具有来源简单、易于自体移植等优点。本研究旨在探讨骨髓间充质干细胞对脑缺血再灌注损伤的保护作用及其可能机制。在短暂性大脑中动脉闭塞（t-MCAO）模型中，在梗死周围皮层观察到过度的氧化应激和肿胀的线粒体增加。静脉注射OM-MSCs可改善线粒体损伤并恢复氧化/抗氧化失衡。利用体外氧葡萄糖剥夺/再灌注（OGD/R）模型，我们发现OGD/R可诱导小鼠神经母细胞瘤N2 a细胞产生过量的活性氧（ROS），并导致线粒体损伤，线粒体膜电位降低，ATP含量减少。OM-MSC transwell共培养减弱了上述干扰，并伴随着UbiA异戊烯基转移酶结构域1（UBIAD 1）表达的增加，而当UBIAD 1被敲低时，OM-MSC的这些保护作用被阻断。UBIAD 1特异性小干扰RNA（siRNA）逆转了由OM-MSCs促进的膜电位和ATP含量的增加。此外，UBIAD 1特异性siRNA阻断了OM-MSC处理的氧化剂/抗氧化剂平衡。总之，我们的研究结果表明，OM-MSCs发挥神经保护作用，在脑I/R损伤，减轻线粒体功能障碍，并通过上调UBIAD 1增强抗氧化作用。
Mesenchymal stem cells (MSCs) have presented a promising neuroprotective effect in cerebral ischemia/reperfusion (I/R). Olfactory mucosa MSCs (OM-MSCs), a novel source of MSCs located in the human nasal cavity, are easy to obtain and situated for autologous transplantation. The present study was designed to evaluate the neuroprotective effects of OM-MSCs on cerebral I/R injury and the possible mechanisms. In the transient middle cerebral artery occlusion (t-MCAO) model, excessive oxidative stress and increased swollen mitochondria were observed in the peri-infarct cortex. Intravenous injection of OM-MSCs ameliorated mitochondrial damage and restored oxidant/antioxidant imbalance. Using the oxygen glucose deprivation/reperfusion (OGD/R) model in vitro, we discovered that the exposure of mouse neuroblastoma N2a cells to OGD/R triggers excessive reactive oxygen species (ROS) generation and induces mitochondrial deterioration with decreased mitochondrial membrane potential and reduces ATP content. OM-MSC transwell coculture attenuated the above perturbations accompanied with increased UbiA prenyltransferase domain-containing 1 (UBIAD1) expression, whereas these protective effects of OM-MSCs were blocked when UBIAD1 was knocked down. UBIAD1-specific small interfering RNA (siRNA) reversed the increased membrane potential and ATP content promoted by OM-MSCs. Additionally, UBIAD1-specific siRNA blocked the oxidant/antioxidant balance treated by OM-MSCs. Overall, our results suggested that OM-MSCs exert neuroprotective effects in cerebral I/R injury by attenuating mitochondrial dysfunction and enhancing antioxidation via upregulation of UBIAD1.
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影响因子：
9
作者：
Fan JR;Lee HT;Lee W;Lin CH;Hsu CY;Hsieh CH;Shyu WC
通讯作者：
Shyu WC
DOI：
10.1002/stem.2578
发表时间：
2017-05
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Garbuzova-Davis S;Haller E;Lin R;Borlongan CV
通讯作者：
Borlongan CV
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
64.8
作者：
CHANCE, B;WILLIAMS, GR
通讯作者：
WILLIAMS, GR
影响因子：
5.6
作者：
Huang, Yan;Hu, Zhiping
通讯作者：
Hu, Zhiping