Exosomes Derived from miR-214-Enriched Bone Marrow-Derived Mesenchymal Stem Cells Regulate Oxidative Damage in Cardiac Stem Cells by Targeting CaMKII.
Exosomes Derived from miR-214-Enriched Bone Marrow-Derived Mesenchymal Stem Cells Regulate Oxidative Damage in Cardiac Stem Cells by Targeting CaMKII.
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富含 miR-214 的骨髓间充质干细胞衍生的外泌体通过靶向 CaMKII 调节心脏干细胞的氧化损伤
DOI：
10.1155/2018/4971261
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发表时间：
2018
影响因子：
--
通讯作者：
Shi B
中科院分区：
文献类型：
--
作者：
Wang Y;Zhao R;Liu D;Deng W;Xu G;Liu W;Rong J;Long X;Ge J;Shi B
心脏干细胞（CSCs）已成为最有前途的心脏保护干细胞之一。最近，人们发现来自骨髓源性间充质干细胞（BMSC）的外泌体通过转运包括微小RNA（miRs）在内的各种生物活性分子来促进细胞增殖和存活。在这项研究中，我们发现BMSC-derived exosomes（BMSC-exos）显着降低氧化应激损伤后CSC的凋亡率和活性氧（ROS）的产生。此外，从缺氧条件下培养的BMSC收集的外泌体（缺氧-外泌体）比从正常条件下培养的BMSC收集的外泌体（Nor-exos）诱导更强的作用。我们还观察到低氧-exos中的miR-214富集程度高于Nor-exos。此外，添加miR-214抑制剂或模拟物以调节BMSC-exos中的miR-214水平，揭示了来自miR-214耗尽的BMSC的外泌体部分逆转了低氧诱导的外泌体对CSC中氧化损伤的影响。这些数据进一步证实了miR-214是BMSC-exos中保护CSC免受氧化损伤的主要效应分子。miR-214模拟物和抑制剂转染测定证实CaMKII是CSC中miR-214的靶基因，外泌体预处理的CSC表现出增加的miR-214水平但降低的CaMKII水平。因此，miR-214/CaMKII轴调节CSC中的氧化应激相关损伤，例如凋亡、钙稳态失衡和过量ROS积累。总的来说，这些发现表明BMSC释放含有miR-214的外泌体，以通过CaMKII沉默来抑制CSC中的氧化应激损伤。
Cardiac stem cells (CSCs) have emerged as one of the most promising stem cells for cardiac protection. Recently, exosomes from bone marrow-derived mesenchymal stem cells (BMSCs) have been found to facilitate cell proliferation and survival by transporting various bioactive molecules, including microRNAs (miRs). In this study, we found that BMSC-derived exosomes (BMSC-exos) significantly decreased apoptosis rates and reactive oxygen species (ROS) production in CSCs after oxidative stress injury. Moreover, a stronger effect was induced by exosomes collected from BMSCs cultured under hypoxic conditions (Hypoxic-exos) than those collected from BMSCs cultured under normal conditions (Nor-exos). We also observed greater miR-214 enrichment in Hypoxic-exos than in Nor-exos. In addition, a miR-214 inhibitor or mimics added to modulate miR-214 levels in BMSC-exos revealed that exosomes from miR-214-depleted BMSCs partially reversed the effects of hypoxia-induced exosomes on oxidative damage in CSCs. These data further confirmed that miR-214 is the main effector molecule in BMSC-exos that protects CSCs from oxidative damage. miR-214 mimic and inhibitor transfection assays verified that CaMKII is a target gene of miR-214 in CSCs, with exosome-pretreated CSCs exhibiting increased miR-214 levels but decreased CaMKII levels. Therefore, the miR-214/CaMKII axis regulates oxidative stress-related injury in CSCs, such as apoptosis, calcium homeostasis disequilibrium, and excessive ROS accumulation. Collectively, these findings suggest that BMSCs release miR-214-containing exosomes to suppress oxidative stress injury in CSCs through CaMKII silencing.
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DOI：
10.1002/stem.2669
发表时间：
2017-10
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Lee WH;Chen WY;Shao NY;Xiao D;Qin X;Baker N;Bae HR;Wei TT;Wang Y;Shukla P;Wu H;Kodo K;Ong SG;Wu JC
通讯作者：
Wu JC
影响因子：
37.8
作者：
Bolli R;Tang XL;Sanganalmath SK;Rimoldi O;Mosna F;Abdel-Latif A;Jneid H;Rota M;Leri A;Kajstura J
通讯作者：
Kajstura J
影响因子：
9.5
作者：
Hong KU;Li QH;Guo Y;Patton NS;Moktar A;Bhatnagar A;Bolli R
通讯作者：
Bolli R
miR-21 通过 PTEN/PI3K/Akt 信号传导减少体外 c-kit( ) 心脏干细胞中过氧化氢诱导的细胞凋亡
影响因子：
--
作者：
Deng W;Wang Y;Long X;Zhao R;Wang Z;Liu Z;Cao S;Shi B
通讯作者：
Shi B
人骨髓间充质干细胞来源的细胞外囊泡促进大鼠心肌梗死模型中的血管生成
影响因子：
4.7
作者：
Bian, Suyan;Zhang, Liping;Yu, Hepeng
通讯作者：
Yu, Hepeng