间充质干细胞分泌的外泌体通过转运miR-125a促进内皮细胞血管生成。

Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a.

作者信息

Liang Xiaolei, Zhang Lina, Wang Shihua, Han Qin, Zhao Robert Chunhua

机构信息

Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China.

Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, People's Republic of China

出版信息

J Cell Sci. 2016 Jun 1;129(11):2182-9. doi: 10.1242/jcs.170373.

Abstract

Angiogenesis plays crucial roles in various physiological processes including wound healing and tissue repair. It requires a tight interaction between endothelial cells and their surrounding environment. Mesenchymal stem cells (MSCs), one of the non-endothelial cell types present in the perivascular environment, have been shown to secret exosomes to modulate intercellular communications between MSCs and their target cells. In this study, we initially isolated exosomes secreted by human adipose-derived MSCs (adMSC-Exo) and examined their roles in angiogenesis. We found that adMSC-Exo could be taken up by endothelial cells and significantly promote angiogenesis in vitro and in vivo Further study showed that miR-125a was enriched in adMSC-Exo, and repressed the expression of the angiogenic inhibitor delta-like 4 (DLL4) by targeting its 3' untranslated region. Additionally, adMSC-Exo and its exosomal transferred miR-125a could repress DLL4 expression and modulate endothelial cell angiogenesis through promoting formation of endothelial tip cells. In conclusion, our study indicates that adMSC-Exo can transfer miR-125a to endothelial cells and promote angiogenesis by repressing DLL4. adMSC-Exo, as a pro-angiogenic factor, might be a promising candidate for therapeutical tissue repair.

摘要

血管生成在包括伤口愈合和组织修复在内的各种生理过程中发挥着关键作用。它需要内皮细胞与其周围环境之间紧密相互作用。间充质干细胞(MSCs)是血管周围环境中存在的非内皮细胞类型之一,已被证明可分泌外泌体来调节MSCs与其靶细胞之间的细胞间通讯。在本研究中,我们首先分离了人脂肪来源的间充质干细胞分泌的外泌体(adMSC-Exo),并研究了它们在血管生成中的作用。我们发现adMSC-Exo可以被内皮细胞摄取,并在体外和体内显著促进血管生成。进一步研究表明,miR-125a在adMSC-Exo中富集,并通过靶向血管生成抑制剂delta样蛋白4(DLL4)的3'非翻译区来抑制其表达。此外,adMSC-Exo及其外泌体转移的miR-125a可以通过促进内皮尖端细胞的形成来抑制DLL4表达并调节内皮细胞血管生成。总之,我们的研究表明,adMSC-Exo可以将miR-125a转移至内皮细胞,并通过抑制DLL4来促进血管生成。adMSC-Exo作为一种促血管生成因子,可能是治疗性组织修复的一个有前景的候选者。

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