Exosomes from microRNA-126 overexpressing mesenchymal stem cells promote angiogenesis by targeting the PIK3R2-mediated PI3K/Akt signalling pathway.
Exosomes from microRNA-126 overexpressing mesenchymal stem cells promote angiogenesis by targeting the PIK3R2-mediated PI3K/Akt signalling pathway.
复制标题
来自microRNA-126过表达间充质干细胞的外泌体通过靶向PIK 3R 2介导的PI 3 K/Akt信号通路促进血管生成
DOI：
10.1111/jcmm.16192
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Zhang L;Ouyang P;He G;Wang X;Song D;Yang Y;He X
microRNA-126（miR-126）是一种内皮特异性miRNA，与血管稳态和血管生成相关。然而，基于miR-126的治疗的效率由于体内miRNA递送的低效率而部分受损。最近，外泌体已经成为治疗性分子递送的天然工具。在此，我们研究了来源于骨髓间充质干细胞（BMMSC）的外泌体是否可以用于递送miR-126以促进血管生成。通过超离心从用miR-126过表达的BMMSC（Exo-miR-126）分离外来体。在体外研究中，Exo-miR-126处理促进了人脐静脉内皮细胞（HUVECs）的增殖、迁移和血管生成。此外，与Exo‐miR‐126孵育后，血管生成相关的血管内皮生长因子（VEGF）和血管紧张素1（Ang‐1）的基因/蛋白表达上调。此外，磷酸肌醇-3激酶调节亚基2（PIK 3R 2）的表达水平与HUVEC中的miR-126呈负相关。特别地，Exo-miR-126处理通过靶向PIK 3R 2以激活PI 3 K/Akt信号传导通路而有助于增强HUVEC的血管生成。同样，Exo-miR-126给药显著增加了伤口部位新形成的毛细血管数量，并加速了体内伤口愈合。结果表明，来源于BMMSC的外泌体与miR-126的组合可能是促进血管生成的有希望的策略。
microRNA‐126 (miR‐126), an endothelial‐specific miRNA, is associated with vascular homeostasis and angiogenesis. However, the efficiency of miR‐126‐based treatment is partially compromised due to the low efficiency of miRNA delivery in vivo. Lately, exosomes have emerged as a natural tool for therapeutic molecule delivery. Herein, we investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) can be utilized to deliver miR‐126 to promote angiogenesis. Exosomes were isolated from BMMSCs overexpressed with miR‐126 (Exo‐miR‐126) by ultracentrifugation. In vitro study, Exo‐miR‐126 treatment promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the gene/protein expression of angiogenesis‐related vascular endothelial growth factor (VEGF) and angiotensin‐1 (Ang‐1) were up‐regulated after incubation with Exo‐miR‐126. Additionally, the expression level of phosphoinositol‐3 kinase regulatory subunit 2 (PIK3R2) showed an inverse correlation with miR‐126 in HUVECs. Particularly, the Exo‐miR‐126 treatment contributed to enhanced angiogenesis of HUVECs by targeting PIK3R2 to activate the PI3K/Akt signalling pathway. Similarly, Exo‐miR‐126 administration profoundly increased the number of newly formed capillaries in wound sites and accelerated the wound healing in vivo. The results demonstrate that exosomes derived from BMMSCs combined with miR‐126 may be a promising strategy to promote angiogenesis.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
影响因子：
3.3
作者：
Huang, Jiang-Hu;Xu, Yang;Lin, Fei-Yue
通讯作者：
Lin, Fei-Yue
丹红注射液通过激活MiR-126/ERK/VEGF通路增强心肌梗死后血管生成
影响因子：
7.5
作者：
Li, Si-Nai;Li, Ping;Liu, Hong-Xu
通讯作者：
Liu, Hong-Xu
MicroRNA-34a 通过靶向 TGFβR2 抑制非小细胞肺癌 H1299 细胞系的增殖并促进其凋亡
影响因子：
--
作者：
Ma, Zhong-Liang;Hou, Pin-Pin;Jin, You-Xin
通讯作者：
Jin, You-Xin