LncRNA-Profile-Based Screening of Extracellular Vesicles Released from Brain Endothelial Cells after Oxygen-Glucose Deprivation.
LncRNA-Profile-Based Screening of Extracellular Vesicles Released from Brain Endothelial Cells after Oxygen-Glucose Deprivation.
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基于lncrna谱的脑内皮细胞在缺氧-葡萄糖剥夺后释放的细胞外囊泡的筛选
DOI：
10.3390/brainsci12081027
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发表时间：
2022-08-03
期刊：
影响因子：
3.3
通讯作者：
Shang, Fei-Fei
中科院分区：
文献类型：
--
作者：
He, Xiang;Zou, Hecun;Lyu, Qiang;Tang, Yujing;Xiong, Wenkui;Shang, Fei-Fei
脑微血管内皮细胞（brain microvascular endothelial cells，BMEC）通过紧密连接相互连接，在脑缺血中发挥重要作用.通过细胞外囊泡（EV）的细胞间信号传导是一种未被充分认识的细胞-细胞串扰模式。本研究旨在探讨长链非编码RNA（lncRNA）在BMEC分泌EV中的潜在功能。我们对原代人类和大鼠BMEC进行了氧气和葡萄糖剥夺（OGD）。富集EV用于RNA测序。测序结果的比较显示，在人类细胞中有146个上调的lncRNA和331个下调的lncRNA，在大鼠细胞中有1215个上调的lncRNA和1200个下调的lncRNA。接下来，我们分析了与染色体上的差异表达（DE）lncRNA共表达的基因，并进行了基因本体（GO）和信号通路富集分析。结果表明，lncRNA可能在细胞凋亡、TNF信号通路和白细胞跨内皮迁移中发挥作用。接下来，使用PCR分析并确认了人类和大鼠之间的三种保守lncRNA。通过RNA pulldown和质谱鉴定这三种lncRNA在人星形胶质细胞中的结合蛋白。这些蛋白可以调节mRNA的稳定性和翻译。此外，慢病毒用于在人小胶质细胞HMC 3细胞中上调它们。结果显示NR_002323.2诱导小胶质细胞M1活化。因此，这些结果表明，BMEC的EV携带lncRNA，其可能调节脑缺血后胶质细胞的功能。
Brain microvascular endothelial cells (BMECs) linked by tight junctions play important roles in cerebral ischemia. Intercellular signaling via extracellular vesicles (EVs) is an underappreciated mode of cell–cell crosstalk. This study aims to explore the potential function of long noncoding RNAs (lncRNAs) in BMECs’ secreted EVs. We subjected primary human and rat BMECs to oxygen and glucose deprivation (OGD). EVs were enriched for RNA sequencing. A comparison of the sequencing results revealed 146 upregulated lncRNAs and 331 downregulated lncRNAs in human cells and 1215 upregulated lncRNAs and 1200 downregulated lncRNAs in rat cells. Next, we analyzed the genes that were coexpressed with the differentially expressed (DE) lncRNAs on chromosomes and performed Gene Ontology (GO) and signaling pathway enrichment analyses. The results showed that the lncRNAs may play roles in apoptosis, the TNF signaling pathway, and leukocyte transendothelial migration. Next, three conserved lncRNAs between humans and rats were analyzed and confirmed using PCR. The binding proteins of these three lncRNAs in human astrocytes were identified via RNA pulldown and mass spectrometry. These proteins could regulate mRNA stability and translation. Additionally, the lentivirus was used to upregulate them in human microglial HMC3 cells. The results showed NR_002323.2 induced microglial M1 activation. Therefore, these results suggest that BMECs’ EVs carry the lncRNAs, which may regulate gliocyte function after cerebral ischemia.
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影响因子：
4.4
作者：
Pivoriunas, Augustas;Verkhratsky, Alexei
通讯作者：
Verkhratsky, Alexei
影响因子：
16
作者：
Dozio V;Sanchez JC
通讯作者：
Sanchez JC
影响因子：
4.1
作者：
Ma L;Bajic VB;Zhang Z
通讯作者：
Zhang Z
DOI：
10.1038/s41580-020-00315-9
发表时间：
2021-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Statello L;Guo CJ;Chen LL;Huarte M
通讯作者：
Huarte M
影响因子：
30.8
作者：
Graham, BH;Waymire, KG;Wallace, DC
通讯作者：
Wallace, DC