Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow.
Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow.
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微血管内皮细胞衍生的微泡通过调节星形胶质细胞和血脑屏障功能以及脑血流来暗示缺血性中风
DOI：
10.1186/s13041-016-0243-1
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发表时间：
2016-06-07
期刊：
影响因子：
3.6
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Pan Q;He C;Liu H;Liao X;Dai B;Chen Y;Yang Y;Zhao B;Bihl J;Ma X
背景内皮细胞（EC）释放的微泡（EMV）可通过传递携带的遗传信息作用于多种靶细胞。星形胶质细胞是脑内血脑屏障（BBB）结构的主要组成部分，参与调节BBB的完整性和血流。内皮细胞和星形胶质细胞之间的相互作用对于BBB在稳态和病理条件下的完整性是必不可少的。在这里，我们研究了人脑微血管内皮细胞释放EMV对星形胶质细胞功能的影响。此外，我们研究了EMV处理的星形胶质细胞对调节血脑屏障功能和脑缺血damage. ResultsEMV从正常条件下培养的EC（n-EMV）或氧和葡萄糖剥夺（OGD-EMV）条件下培养的星形胶质细胞有不同的影响。n-EMV通过调节PI 3 K/Akt信号通路促进星形胶质细胞增殖，而OGD-EMV通过调节PI 3 K/Akt信号通路抑制星形胶质细胞增殖。胶质细胞酸性蛋白（GFAP）表达（星形胶质细胞活化的标志物）被n-EMV上调，而被OGD-EMV下调。同时，n-EMV抑制而OGD-EMV促进星形胶质细胞凋亡，并上调/下调Caspase-9和Bcl-2的表达。在内皮细胞-星形胶质细胞共培养的血脑屏障模型中，与OGD-EMV相反，n-EMV降低血脑屏障的通透性，同时上调悬韧带-1（ZO-1）和Claudin-5。在短暂性脑缺血小鼠模型中，n-EMV改善，而OGD-EMV加重，血脑屏障破坏，局部脑血流量（CBF）减少，梗死体积和神经功能缺损score.ConclusionsOur数据表明，EMV dilateral调节星形胶质细胞的功能，血脑屏障的完整性和CBF，并可以作为一个新的治疗缺血性中风的目标。
BackgroundEndothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage.ResultsEMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up-regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs-astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score.ConclusionsOur data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke.