Department of Emergency, The First People's Hospital of Wenling, Wenling 317500, China.
Department of Neurology, The First People's Hospital of Wenling, Wenling 317500, China.
Neuroscience. 2021 Nov 10;476:34-44. doi: 10.1016/j.neuroscience.2021.08.026. Epub 2021 Sep 3.
Exosomes might mediate the effects of remote ischemic post-conditioning (RIPostC) treatment on vital organs. The present study aimed to explore the role of RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) in the effects of human umbilical vein endothelial cell (HUVEC)-derived exosomes on ischemic injuries in vitro and in vivo. HUVECs were subjected to oxygen-glucose deprivation (OGD) treatment and exosomes were collected OGD-treated human neural cells were incubated with HUVEC-derived exosomes. Changes in cell viability, apoptosis, and RMRP-mediated PI3K/Akt/mTOR pathway activity were detected. The role of RMRP inhibition in the anti-OGD effects of exosomes was further determined by upregulating RMRP expression in human neural cells. The potential RMRP inhibitory factors in exosomes were explored using microarray detection. The effects of exosomes were validated with MCAO mouse models. In OGD neurons incubated with the exosomes, cell viability was improved and cell apoptosis was suppressed. At molecular level, exosomes on downregulated RMRP, p-PI3K, p-Akt, and p-mTOR, while induced eNOS. After the overexpression of RMRP, the cell protective effects of exosomes were counteracted, which was associated with the re-activation of PI3K/Akt/mTOR pathway. Based on the detection of microarray, the induced levels of miR-206 and miR-1-3p by OGD in HVUECs contributed to the RMPR inhibition. Additionally, injection of exosomes restricted infarction area and suppressed RMRP in MCAO mice. Collectively, exosomes from OGD HUVECs could protect neurons against ischemia-induced injuries, and the effects were associated with the suppression of RMRP in neurons via distance transfer of miR-206 and miR-1-3p.
外泌体可能介导远程缺血后处理（RIPostC）治疗对重要器官的影响。本研究旨在探讨线粒体 RNA 加工内切核糖核酸酶（RMRP）的 RNA 成分在人脐静脉内皮细胞（HUVEC）衍生的外泌体对体外和体内缺血损伤中的作用。将 HUVEC 进行氧葡萄糖剥夺（OGD）处理，并收集外泌体。用 OGD 处理的人神经细胞孵育 HUVEC 衍生的外泌体，检测细胞活力、凋亡和 RMRP 介导的 PI3K/Akt/mTOR 通路活性的变化。通过上调人神经细胞中的 RMRP 表达，进一步确定 RMRP 抑制在 exosomes 抗 OGD 作用中的作用。使用微阵列检测探索外泌体中的潜在 RMRP 抑制因子。通过 MCAO 小鼠模型验证外泌体的作用。在与外泌体孵育的 OGD 神经元中，细胞活力得到改善，细胞凋亡受到抑制。在分子水平上，外泌体下调 RMRP、p-PI3K、p-Akt 和 p-mTOR，同时诱导 eNOS。RMRP 过表达后，外泌体的细胞保护作用被抵消，这与 PI3K/Akt/mTOR 通路的重新激活有关。基于微阵列的检测，OGD 在 HVUEC 中诱导的 miR-206 和 miR-1-3p 水平有助于 RMPR 抑制。此外，外泌体的注射限制了 MCAO 小鼠的梗塞面积，并抑制了 MCAO 小鼠的 RMRP。总之，来自 OGD HUVEC 的外泌体可以保护神经元免受缺血性损伤，其作用与通过 miR-206 和 miR-1-3p 的远距离转移抑制神经元中的 RMRP 有关。
