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脑缺血再灌注损伤大鼠模型中N6-甲基腺苷mRNA甲基化的改变

Alteration of -Methyladenosine mRNA Methylation in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

作者信息

Yi Dazhuang, Wang Qunhui, Zhao Yuhao, Song Yu, You Hong, Wang Jian, Liu Renjie, Shi Zhongqiang, Chen Xuan, Luo Qi

机构信息

Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.

Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Front Neurosci. 2021 Mar 16;15:605654. doi: 10.3389/fnins.2021.605654. eCollection 2021.

Abstract

AIM

This study was conducted in order to reveal the alterations in the -methyladenosine (m6A) modification profile of cerebral ischemia-reperfusion injury model rats.

MATERIALS AND METHODS

Rats were used to establish the middle cerebral artery occlusion and reperfusion (MCAO/R) model. MeRIP-seq and RNA-seq were performed to identify differences in m6A methylation and gene expression. The expression of m6A methylation regulators was analyzed in three datasets and detected by quantitative real-time polymerase chain reaction, western blot, and immunofluorescence.

RESULTS

We identified 1,160 differentially expressed genes with hypermethylated or hypomethylated m6A modifications. The differentially expressed genes with hypermethylated m6A modifications were involved in the pathways associated with inflammation, while hypomethylated differentially expressed genes were related to neurons and nerve synapses. Among the m6A regulators, FTO was specifically localized in neurons and significantly downregulated after MCAO/R.

CONCLUSION

Our study provided an m6A transcriptome-wide map of the MACO/R rat samples, which might provide new insights into the mechanisms of cerebral ischemia-reperfusion injury.

摘要

目的

本研究旨在揭示脑缺血再灌注损伤模型大鼠的N6-甲基腺苷(m6A)修饰谱的变化。

材料与方法

采用大鼠建立大脑中动脉闭塞再灌注(MCAO/R)模型。进行MeRIP-seq和RNA-seq以鉴定m6A甲基化和基因表达的差异。在三个数据集中分析m6A甲基化调节因子的表达,并通过定量实时聚合酶链反应、蛋白质免疫印迹和免疫荧光进行检测。

结果

我们鉴定出1160个具有m6A修饰高甲基化或低甲基化的差异表达基因。m6A修饰高甲基化的差异表达基因参与了与炎症相关的通路,而低甲基化的差异表达基因与神经元和神经突触有关。在m6A调节因子中,FTO特异性定位于神经元,并且在MCAO/R后显著下调。

结论

我们的研究提供了MACO/R大鼠样本的全转录组m6A图谱,这可能为脑缺血再灌注损伤的机制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb3/8009187/d79d98997595/fnins-15-605654-g001.jpg

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