Detection and analysis of apoptosis- and autophagy-related miRNAs of mouse vascular endothelial cells in chronic intermittent hypoxia model
Detection and analysis of apoptosis- and autophagy-related miRNAs of mouse vascular endothelial cells in chronic intermittent hypoxia model
复制标题
慢性间歇性缺氧模型小鼠血管内皮细胞凋亡和自噬相关miRNA的检测与分析
DOI：
10.1016/j.lfs.2017.11.001
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发表时间：
2018-01-15
期刊：
影响因子：
6.1
通讯作者：
Lin, Qi-Chang
中科院分区：
文献类型：
--
作者：
Liu, Kai-Xiong;Chen, Gong-Ping;Lin, Qi-Chang
内皮功能障碍是阻塞性睡眠呼吸暂停/低通气综合征（OSAHS）引起的心血管并发症的主要致病机制。慢性间歇性缺氧（CIH）是OSAHS相关内皮功能障碍的主要因素。缺氧诱导因子（HIF）通路调节下游靶基因的表达并介导CIH诱导的内皮损伤引起的细胞凋亡。 miRNA 在转录后水平的这一过程中发挥着广泛而重要的负调控作用。然而，miRNA在CIH组织模型中的调控机制仍不清楚。本研究建立了CIH的小鼠主动脉内皮细胞模型，试图通过miRNA芯片分析筛选出特定的miRNA。结果发现14个miRNA存在差异表达。其中6个存在显着差异，并通过实时定量PCR（Q-PCR）验证，其中4个显着上调，2个显着下调。为了获得关于改变的 miRNA 的后续调控的公正的全局视角，我们通过 GO 建立了信号网络来预测 6 个 miRNA 的靶基因。结果发现，6个鉴定出的miRNA是凋亡或自噬相关的靶基因。 miR-193 的下调可抑制 CIH 诱导的内皮损伤和细胞凋亡或自噬相关蛋白的表达。总之，我们的结果表明 CIH 可以诱导 miRNA 的差异表达，并且 miRNA 表达模式的改变与凋亡或自噬相关基因的表达相关。
Endothelial dysfunction is the main pathogenic mechanism of cardiovascular complications induced by obstructive sleep apnea/hyponea syndrome (OSAHS). Chronic intermittent hypoxia (CIH) is the primary factor of OSAHS-associated endothelial dysfunction. The hypoxia inducible factor (HIF) pathway regulates the expression of downstream target genes and mediates cell apoptosis caused by CIH-induced endothelial injury. miRNAs play extensive and important negative regulatory roles in this process at the post-transcriptional level. However, the regulatory mechanism of miRNAs in CIH tissue models remains unclear. The present study established a mouse aortic endothelial cell model of CIH in an attempt to screen out specific miRNAs by using miRNA chip analysis. It was found that 14 miRNAs were differentially expressed. Of them, 6 were significantly different and verified by quantitative real-time PCR (Q-PCR), of which four were up-regulated and two were down-regulated markedly. To gain an unbiased global perspective on subsequent regulation by altered miRNAs, we established signaling networks by GO to predict the target genes of the 6 miRNAs. It was found that the 6 identified miRNAs were apoptosis-or autophagy-related target genes. Down-regulation of miR-193 inhibits CIH induced endothelial injury and apoptosis-or autophagy-related protein expression. In conclusion, our results showed that CIH could induce differential expression of miRNAs, and alteration in the miRNA expression pattern was associated with the expression of apoptosis-or autophagy-related genes.