FTO-dependent m 6 A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke.
Bin LiWen XiYing BaiXue LiuYuan ZhangLu LiLiang BianChenchen LiuYing TangLing ShenLi YangXiaochun GuJian XieZhongqiu ZhouYu WangXiaoyu YuJianhong WangJie ChaoBing HanHonghong YaoPublished in: Nature communications (2023)
Vascular repair is considered a key restorative measure to improve long-term outcomes after ischemic stroke. N 6 -methyladenosine (m 6 A), the most prevalent internal modification in eukaryotic mRNAs, functionally mediates vascular repair. However, whether circular RNA SCMH1 (circSCMH1) promotes vascular repair by m 6 A methylation after stroke remains to be elucidated. Here, we identify the role of circSCMH1 in promoting vascular repair in peri-infarct cortex of male mice and male monkeys after photothrombotic (PT) stroke, and attenuating the ischemia-induced m 6 A methylation in peri-infarct cortex of male mice after PT stroke. Mechanically, circSCMH1 increased the translocation of ubiquitination-modified fat mass and obesity-associated protein (FTO) into nucleus of endothelial cells (ECs), leading to m 6 A demethylation of phospholipid phosphatase 3 (Plpp3) mRNA and subsequently the increase of Plpp3 expression in ECs. Our data demonstrate that circSCMH1 enhances vascular repair via FTO-regulated m 6 A methylation after stroke, providing insights into the mechanism of circSCMH1 in promoting stroke recovery.
Keyphrases
- atrial fibrillation
- endothelial cells
- dna methylation
- metabolic syndrome
- acute myocardial infarction
- transcription factor
- insulin resistance
- functional connectivity
- machine learning
- physical activity
- body mass index
- acute coronary syndrome
- binding protein
- left ventricular
- deep learning
- percutaneous coronary intervention
- coronary artery disease
- electronic health record
- vascular endothelial growth factor
- big data
- high fat diet induced