实用医学杂志2023，Vol.39Issue(21)：2754-2760,7.DOI:10.3969/j.issn.1006-5725.2023.21.011
Mettl14介导的m6A修饰对改善心肌梗死的分子机制
Molecular mechanism of Mettl14 mediated m6A modification in improving myocardial infarction
摘要
Abstract
Objective To investigate the biological role of methyltransferase-like 14(METTL14)-medi-ated m6A modification in myocardial infarction(MI).Methods A total of 40 mice were randomly divided into 4 groups:Sham+AAV9-NC group(n = 10),Sham+AAV9-METTL14 group(n = 10),MI+AAV9-NC group(n = 10)and MI+AAV9-METTL14 group(n = 10).Mice in each group were injected with AAV9-METTL14 or AAV9-NC through the tail vein one week before MI induction.Cardiac function was measured non-invasively by transthoracic echocardiography,and microvascular injury were measured by immunofluorescence.CMECs were isolated from mouse myocardial tissue,and the cells were treated with oxygen-glucose deprivation(OGD).Results METTL14 was downregulated in MI mouse heart tissue as well as in OGD-treated CMECs.Compared with the Sham+AAV9-NC group,the expression of VE-cadherin was significantly down-regulated(P<0.05),ROS levels increased signifi-cantly(P<0.05)in the MI+AAV9-NC group.MI+AAV9-METTL14 suppressed these changes and enhanced cardiac function in mice.Compared with the NC group,a significant increase in mitochondrial ROS levels was observed in the OGD group(P<0.05).Knockdown of METTL14 in CMECs exacerbated ROS levels(P<0.05),and the addition of USP48 overexpression plasmid reversed these changes(P<0.05).Conclusion METTL14 was lowly expressed in MI and mediates mitochondrial dysfunction in CMECs by increasing the m6A modification level of USP48 in CMECs to reduce its stability.关键词
甲基转移酶样14/N6-甲基腺苷/心肌梗死/泛素特异性肽酶48Key words
methyltransferase-like 14/N6-methyladenosine/myocardial infarction/ubiquitin-specific peptidase 48分类
医药卫生引用本文复制引用
郑学斌,沙莎,杨慧琼,刘恋..Mettl14介导的m6A修饰对改善心肌梗死的分子机制[J].实用医学杂志,2023,39(21):2754-2760,7.基金项目
湖南省卫生健康委员会科研项目(编号:20210278) （编号:20210278）
