当前位置: X-MOL 学术Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity.
Cell Research ( IF 44.1 ) Pub Date : 2017-Jul-01 , DOI: 10.1038/cr.2017.62
Bing Xu , Yu Zhang , Xu-Fei Du , Jia Li , Hua-Xing Zi , Ji-Wen Bu , Yong Yan , Hua Han , Jiu-Lin Du

Vascular integrity helps maintain brain microenvironment homeostasis, which is critical for the normal development and function of the central nervous system. It is known that neural cells can regulate brain vascular integrity. However, due to the high complexity of neurovascular interactions involved, understanding of the neural regulation of brain vascular integrity is still rudimentary. Using intact zebrafish larvae and cultured rodent brain cells, we find that neurons transfer miR-132, a highly conserved and neuron-enriched microRNA, via secreting exosomes to endothelial cells (ECs) to maintain brain vascular integrity. Following translocation to ECs through exosome internalization, miR-132 regulates the expression of vascular endothelial cadherin (VE-cadherin), an important adherens junction protein, by directly targeting eukaryotic elongation factor 2 kinase (eef2k). Disruption of neuronal miR-132 expression or exosome secretion, or overexpression of vascular eef2k impairs VE-cadherin expression and brain vascular integrity. Our study indicates that miR-132 acts as an intercellular signal mediating neural regulation of the brain vascular integrity and suggests that the neuronal exosome is a novel avenue for neurovascular communication.

中文翻译:

神经元分泌含有miR-132的外来体来调节脑血管的完整性。

血管完整性有助于维持大脑微环境的动态平衡,这对于中枢神经系统的正常发育和功能至关重要。众所周知,神经细胞可以调节脑血管的完整性。然而,由于所涉及的神经血管相互作用的高度复杂性,对脑血管完整性的神经调节的理解仍然是基本的。使用完整的斑马鱼幼虫和培养的啮齿动物脑细胞,我们发现神经元通过将外泌体分泌到内皮细胞(ECs)来维持大脑血管的完整性,从而转移了miR-132,miR-132是高度保守且富含神经元的microRNA。通过外泌体内化转位至EC后,miR-132调节血管内皮钙黏着蛋白(VE-cadherin)(一种重要的黏附连接蛋白)的表达,通过直接靶向真核延伸因子2激酶(eef2k)。神经元miR-132表达或外泌体分泌的破坏,或血管eef2k的过度表达会损害VE-钙黏着蛋白表达和脑血管完整性。我们的研究表明,miR-132充当介导大脑血管完整性的神经调节的细胞间信号,并暗示神经元外泌体是神经血管通讯的新途径。
更新日期:2017-07-22
down
wechat
bug