Stress conditions induced circRNAs profile of extracellular vesicles in brain microvascular endothelial cells
Stress conditions induced circRNAs profile of extracellular vesicles in brain microvascular endothelial cells
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DOI：
10.1007/s11011-022-01025-1
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发表时间：
2022-06-14
影响因子：
3.6
通讯作者：
Shang，Fei-Fei
中科院分区：
文献类型：
--
作者：
Min，Xiao-Li;Zou，Hecun;Shang，Fei-Fei
脑缺血引起缺氧性损伤和炎症反应，脑微血管内皮细胞（BMVECs）功能障碍是血脑屏障破坏的初始阶段。内皮细胞分泌参与细胞间信号转导的细胞外囊泡（EV）。EV含有多种RNA、蛋白质和代谢物。环状RNA（circRNA）是非编码RNA的一员。circRNA在BMVEC中的表达谱和潜在功能尚不清楚。在这里，人BMVEC经历缺氧或TNF-α诱导，并通过RNA测序测量circRNA的变化。共有70个circRNA显示差异表达，包括43个先前未记录的circRNA和27个记录的circRNA。由于星形胶质细胞末端足包围内皮细胞，它们被认为是来自BMVEC的EV的主要靶点。利用miRNA序列数据和生物信息学方法预测星形胶质细胞中的circRNA-miRNA-mRNA网络。基因本体（GO）分析表明circRNA的主要下游靶点是DNA转录调控和蛋白激酶相关的信号通路。这些结果表明，改变circRNA可能是脑缺血诱导的缺氧损伤和炎症的潜在治疗靶点。
Cerebral ischemia causes hypoxic injury and inflammation, and brain microvascular endothelial cells (BMVECs) dysfunction is an initial stage of blood-brain barrier disruption. Endothelial cells secrete extracellular vesicles (EVs) that are involved in intercellular signal transduction. EVs contain a variety of RNAs, proteins, and metabolites. Circular RNA (circRNA) is a member of the non-coding RNA. The expression profile and potential function of circRNAs in BMVECs are unknown. Here, human BMVECs have undergone hypoxia or TNF-α induction, and the changes in circRNAs were measured by RNA sequencing. A total of 70 circRNAs showed differential expression, including 43 previously unrecorded circRNAs and 27 recorded circRNAs. Since astrocyte end-feet encircle endothelial cells, they are considered the main targets of the EVs from BMVEC. The miRNA sequence data and bioinformatics were used to predict the circRNA-miRNA-mRNA networks in astrocytes. The gene ontology (GO) analysis showed the main downstream targets of circRNAs are DNA transcription regulation and protein kinase-related signaling pathways. These results suggest that altering circRNAs may be a potential therapeutic target for cerebral ischemia induced hypoxic injury and inflammation.