外泌体来源的间充质干细胞微小 RNA-93 减轻新生鼠缺氧缺血性脑损伤。
microRNA-93 packaged in extracellular vesicles from mesenchymal stem cells reduce neonatal hypoxic-ischemic brain injury.
机构信息
Department of Medical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China; Medical College of Guangxi University, Nanning 530004, Guangxi, China.
Department of Ultrasound, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
出版信息
Brain Res. 2022 Nov 1;1794:148042. doi: 10.1016/j.brainres.2022.148042. Epub 2022 Aug 8.
OBJECTIVE
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been proposed as a promising strategy for treating ischemia-related diseases. Herein, we probed into the role of miR-93 delivered by BMSC-EVs in hypoxic-ischemic brain injury (HIBD).
METHODS
Neonatal HIBD mouse models and hippocampal neuron models of oxygen glucose deprivation (OGD) were constructed. EVs were isolated from the culture medium of bone marrow MSCs (BMSCs). After co-culture of BMSC-EVs with OGD-exposed hippocampal neurons, the effect of microRNA-93 (miR-93) delivered by BMSC-EVs on OGD-induced hippocampal neurons as well as on HIBD in vivo under transfection of miR-93 mimic or inhibitor was explored. The interaction among miR-93, JMJD3, and p53/KLF2 axis was assessed.
RESULTS
BMSC-EVs prevented OGD-induced hippocampal neuron apoptosis and inflammation, which was associated with their transfer of miR-93 into the hippocampal neurons. miR-93 targeted JMJD3 and downregulated its expression, thus inhibiting the OGD-induced hippocampal neuron apoptosis. By regulating the JMJD3/p53/KLF2 axis, miR-93 in BMSC-EVs reduced the OGD-induced hippocampal neuron apoptosis in vitro as well as alleviating HIBD in vivo.
CONCLUSIONS
The current study highlighted that miR-93 delivered by BMSC-EVs alleviated HIBD in neonatal mice through the JMJD3-dependent p53/KLF2 axis.
目的
间充质干细胞衍生的细胞外囊泡（MSC-EVs）被认为是治疗与缺血相关疾病的有前途的策略。在此，我们探讨了骨髓间充质干细胞衍生的 EVs 中 miR-93 在缺氧缺血性脑损伤（HIBD）中的作用。
方法
构建新生 HIBD 小鼠模型和氧葡萄糖剥夺（OGD）海马神经元模型。从骨髓间充质干细胞（BMSCs）的培养基中分离 EVs。BMSC-EVs 与 OGD 暴露的海马神经元共培养后，通过转染 miR-93 模拟物或抑制剂，研究 BMSC-EVs 传递的 miR-93 对 OGD 诱导的海马神经元以及体内 HIBD 的影响。评估 miR-93、JMJD3 和 p53/KLF2 轴之间的相互作用。
结果
BMSC-EVs 可预防 OGD 诱导的海马神经元凋亡和炎症，这与其将 miR-93 转移到海马神经元有关。miR-93 靶向 JMJD3 并下调其表达，从而抑制 OGD 诱导的海马神经元凋亡。通过调节 JMJD3/p53/KLF2 轴，BMSC-EVs 中的 miR-93 减少了体外 OGD 诱导的海马神经元凋亡，并减轻了体内 HIBD。
结论
本研究强调了 BMSC-EVs 传递的 miR-93 通过 JMJD3 依赖的 p53/KLF2 轴缓解新生小鼠的 HIBD。
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