Liu Hua, Wang Jinju, Chen Yusen, Chen Yanfang, Ma Xiaotang, Bihl Ji C, Yang Yi
College of Health Science, Wuhan Sports University, Wuhan 430079, China.
Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA.
Oxid Med Cell Longev. 2017;2017:9397631. doi: 10.1155/2017/9397631. Epub 2017 May 28.
We have demonstrated that neural progenitor cells (NPCs) protect endothelial cells (ECs) from oxidative stress. Since exosomes (EXs) can convey the benefit of parent cells through their carried microRNAs (miRs) and miR-210 is ubiquitously expressed with versatile functions, we investigated the role of miR-210 in the effects of NPC-EXs on oxidative stress and dysfunction in ECs. NPCs were transfected with control and miR-210 scramble/inhibitor/mimic to generate NPC-EXs, NPC-EXs, NPC-EXs, and NPC-EXs. The effects of various NPC-EXs on angiotensin II- (Ang II-) induced reactive oxygen species (ROS) overproduction, apoptosis, and dysfunction, as well as dysregulation of Nox2, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 in ECs were evaluated. Results showed (1) Ang II-induced ROS overproduction, increase in apoptosis, and decrease in tube formation ability, accompanied with Nox2 upregulation and reduction of p-VEGFR2/VEGFR2 in ECs. (2) Compared to NPC-EXs or NPC-EXs, NPC-EXs were less whereas NPC-EXs were more effective on attenuating these detrimental effects induced by Ang II in ECs. (3) These effects of NPC-EXs and NPC-EXs were associated with the changes of miR-210, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 ratio in ECs. Altogether, the protective effects of NPC-EXs on Ang II-induced endothelial injury through miR-210 which controls Nox2/ROS and VEGF/VEGFR2 signals were studied.
我们已经证明神经祖细胞（NPCs）可保护内皮细胞（ECs）免受氧化应激。由于外泌体（EXs）能够通过其所携带的微小RNA（miRs）传递亲代细胞的益处，且miR-210广泛表达并具有多种功能，因此我们研究了miR-210在NPC-EXs对ECs氧化应激和功能障碍影响中的作用。用对照和miR-210干扰/抑制剂/模拟物转染NPCs以产生NPC-EXs、NPC-EXs、NPC-EXs和NPC-EXs。评估了各种NPC-EXs对血管紧张素II（Ang II）诱导的活性氧（ROS）过量产生、细胞凋亡和功能障碍，以及ECs中Nox2、ephrin A3、血管内皮生长因子（VEGF）和磷酸化血管内皮生长因子受体2（p-VEGFR2）/血管内皮生长因子受体2（VEGFR2）失调的影响。结果显示：（1）Ang II诱导ECs中ROS过量产生、细胞凋亡增加以及管形成能力降低，同时伴有Nox2上调和p-VEGFR2/VEGFR2降低。（2）与NPC-EXs或NPC-EXs相比，NPC-EXs在减轻Ang II诱导的ECs这些有害影响方面效果较差，而NPC-EXs效果更佳。（3）NPC-EXs和NPC-EXs的这些作用与ECs中miR-210、ephrin A3、VEGF和p-VEGFR2/VEGFR2比值的变化有关。总之，研究了NPC-EXs通过控制Nox2/ROS和VEGF/VEGFR2信号的miR-210对Ang II诱导的内皮损伤的保护作用。
