Li Yu-Ning, Liang Ya-Ping, Zhang Jing-Qian, Li Na, Wei Zhi-Yuan, Rao Yijian, Chen Jian-Huan, Jin Yun-Yun
School of Biotechnology, Jiangnan University, Wuxi, China.
Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
Front Neurosci. 2024 Aug 2;18:1435185. doi: 10.3389/fnins.2024.1435185. eCollection 2024.
The activation of cerebral endothelial cells (CECs) has recently been reported to be the earliest acute neuroinflammation event in the CNS during sepsis-associated encephalopathy (SAE). Importantly, adenosine-to-inosine (A-to-I) RNA editing mediated by ADARs has been associated with SAE, yet its role in acute neuroinflammation in SAE remains unclear.
Our current study systematically analyzed A-to-I RNA editing in cerebral vessels, cerebral endothelial cells (CECs), and microglia sampled during acute neuroinflammation after treatment in a lipopolysaccharide (LPS)-induced SAE mouse model.
Our results showed dynamic A-to-I RNA editing activity changes in cerebral vessels during acute neuroinflammation. Differential A-to-I RNA editing (DRE) associated with acute neuroinflammation were identified in these tissue or cells, especially missense editing events such as S367G in antizyme inhibitor 1 () and editing events in lincRNAs such as maternally expressed gene 3 (), , and macrophage M2 polarization regulator (). Importantly, geranylgeranyl diphosphate synthase 1 () and another three genes were differentially edited across cerebral vessels, CECs, and microglia. Notably, Spearman correlation analysis also revealed dramatic time-dependent DRE during acute neuroinflammation, especially in GTP cyclohydrolase1 () and non-coding RNA activated by DNA damage (), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs.
The findings in our current study demonstrate substantial A-to-I RNA editing changes during acute neuroinflammation in SAE, underlining its potential role in the disease.
最近有报道称，在脓毒症相关性脑病（SAE）期间，脑内皮细胞（CEC）的激活是中枢神经系统（CNS）中最早发生的急性神经炎症事件。重要的是，由ADARs介导的腺苷到肌苷（A-to-I）RNA编辑与SAE有关，但其在SAE急性神经炎症中的作用仍不清楚。
我们目前的研究系统地分析了在脂多糖（LPS）诱导的SAE小鼠模型中，急性神经炎症治疗后，在脑血管、脑内皮细胞（CEC）和小胶质细胞中采样的A-to-I RNA编辑情况。
我们的结果显示，在急性神经炎症期间，脑血管中A-to-I RNA编辑活性发生动态变化。在这些组织或细胞中发现了与急性神经炎症相关的差异A-to-I RNA编辑（DRE），特别是错义编辑事件，如抗酶抑制剂1中的S367G，以及长链非编码RNA中的编辑事件，如母源表达基因3、和巨噬细胞M2极化调节剂。重要的是，香叶基香叶基二磷酸合酶1和另外三个基因在脑血管、CEC和小胶质细胞中存在差异编辑。值得注意的是，Spearman相关性分析还显示，在急性神经炎症期间，特别是在GTP环化水解酶1和DNA损伤激活的非编码RNA中，存在显著的时间依赖性DRE，两者的编辑水平与LPS治疗后的时间以及脑血管和CEC中编辑基因的表达均呈正相关。
我们目前研究的结果表明，在SAE急性神经炎症期间，A-to-I RNA编辑发生了实质性变化，突显了其在该疾病中的潜在作用。
