Exosomes Derived from CXCR4-Overexpressing BMSC Promoted Activation of Microvascular Endothelial Cells in Cerebral Ischemia/Reperfusion Injury.
Exosomes Derived from CXCR4-Overexpressing BMSC Promoted Activation of Microvascular Endothelial Cells in Cerebral Ischemia/Reperfusion Injury.
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DOI：
10.1155/2020/8814239
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发表时间：
2020
影响因子：
3.1
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Li X;Zhang Y;Wang Y;Zhao D;Sun C;Zhou S;Xu D;Zhao J
缺血性卒中是一种严重的急性脑血管疾病，早期神经保护治疗可改善病情。然而，由于缺乏有效的神经保护药物，大多数中风患者都有不同程度的长期残疾。在本研究中，我们研究了CXCR4过表达的BMSCs来源的外体在缺血性脑梗塞后血管功能恢复和神经修复中的作用。将CXCR4编码的慢病毒(BMSCCXCR4)导入BMSCs。分离了来源于BMSCCXCR4(ExoCXCR4)的外切体，并用透射电子显微镜和动态光散射法对其进行了表征。用免疫印迹和定量聚合酶链式反应分析CXCR4在BMSCs和外体中的表达。建立大鼠大脑中动脉闭塞(MCAO)模型，注射ExoCXCR4，观察其行为学变化。体外检测ExoCXCR4促进血管生成的增殖和管状形成以及对脑血管内皮细胞的保护作用。与对照组相比，ExoCXCR4组在缺血再灌注后7 d、14 d和21 d的mNSS评分显著降低(P<0.05)。ExoCXCR4组bEnd.3细胞的增殖能力强于其他组(P<；0.05)，而CXCR4抑制剂可减弱这一作用。外切体对照(ExoCon)能显著促进bEnd.3细胞的迁移(P<；0.05)，而ExoCXCR4组和ExoCon组之间无显著差异(P>；0.05)。与ExoCon组相比，ExoCXCR4能进一步促进血管内皮细胞的增殖和管状生成(P<；0.05)。此外，氯化钴(CoCl2)可促进β-连环蛋白和WNT-3的表达，而ExoCon可降低这些蛋白的表达(P<；0.05)。ExoCXCR4可进一步减弱WNT-3a/β-连环蛋白通路的激活(P<；0.05)。在缺血再灌注损伤中，ExoCXCR4通过Wnt-3a/β-catenin途径促进微血管内皮细胞的增殖和管状形成，发挥抗细胞凋亡作用。
Ischemic stroke is a severe acute cerebrovascular disease which can be improved with neuroprotective therapies at an early stage. However, due to the lack of effective neuroprotective drugs, most stroke patients have varying degrees of long-term disability. In the present study, we investigated the role of exosomes derived from CXCR4-overexpressing BMSCs in restoring vascular function and neural repair after ischemic cerebral infarction. BMSCs were transfected with lentivirus encoded by CXCR4 (BMSCCXCR4). Exosomes derived from BMSCCXCR4 (ExoCXCR4) were isolated and characterized by transmission electron microscopy and dynamic light scattering. Western blot and qPCR were used to analyze the expression of CXCR4 in BMSCs and exosomes. The acute middle cerebral artery occlusion (MCAO) model was prepared, ExoCXCR4 were injected into the rats, and behavioral changes were analyzed. The role of ExoCXCR4 in promoting the proliferation and tube formation for angiogenesis and protecting brain endothelial cells was determined in vitro. Compared with the control groups, the ExoCXCR4 group showed a significantly lower mNSS score at 7 d, 14 d, and 21 d after ischemia/reperfusion (P < 0.05). The bEnd.3 cells in the ExoCXCR4 group have stronger proliferation ability than other groups (P < 0.05), while the CXCR4 inhibitor can reduce this effect. Exosomes control (ExoCon) can significantly promote the migration of bEnd.3 cells (P < 0.05), while there was no significant difference between the ExoCXCR4 and ExoCon groups (P > 0.05). ExoCXCR4 can further promote the proliferation and tube formation for the angiogenesis of the endothelium compared with ExoCon group (P < 0.05). In addition, cobalt chloride (COCl2) can increase the expression of β-catenin and Wnt-3, while ExoCon can reduce the expression of these proteins (P < 0.05). ExoCXCR4 can further attenuate the activation of Wnt-3a/β-catenin pathway (P < 0.05). In ischemia/reperfusion injury, ExoCXCR4 promoted the proliferation and tube formation of microvascular endothelial cells and play an antiapoptotic role via the Wnt-3a/β-catenin pathway.
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影响因子：
3.1
作者：
Marti-Fabregas, Joan;Crespo, Javier;Delgado-Mederos, Raquel;Martinez-Ramirez, Sergi;Pena, Esther;Marin, Rebeca;Dinia, Lavinia;Jimenez-Xarrie, Elena;Fernandez-Arcos, Ana;Perez-Perez, Jesus;Querol, Luis;Suarez-Calvet, Marc;Badimon, Lina
通讯作者：
Badimon, Lina
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/s0140-6736(17)32152-9
发表时间：
2017-09-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2016 Causes of Death Collaborators
通讯作者：
GBD 2016 Causes of Death Collaborators
影响因子：
8.3
作者：
Chen J;Chopp M
通讯作者：
Chopp M
大鼠脂肪衍生的间充质干细胞的外泌体对挤压损伤后神经突生长和坐骨神经再生的影响。
影响因子：
5.1
作者：
Bucan V;Vaslaitis D;Peck CT;Strauß S;Vogt PM;Radtke C
通讯作者：
Radtke C