Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.
Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.
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缺血后处理通过 miR-181a-2-3p 的转录和表观遗传调控预防老年心肌缺血/再灌注损伤
DOI：
10.1155/2022/9635674
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发表时间：
2022
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
缺血后处理（Ischemic postconditioning，IPostC）被认为是减轻缺血/再灌注（ischemic/reperfusion，I/R）损伤的一种策略，自噬参与了I/R诱导的老年心肌损伤，但IPostC调控自噬的机制尚不清楚。在这里，我们在老年心肌细胞中实施了miRNA测序分析，以确定HPostC后新的miR-181 a-2- 3 p，其通过靶向老年心肌中的AMBRA 1来抑制自噬，以保护I/R诱导的老年心肌损伤。从机制上讲，我们发现IPostC可以诱导miR-181 a-2- 3 p启动子的DNA低甲基化和H3 K14高乙酰化，这是由于DNMT 3b和HDAC 2在其启动子处的结合减少，这有助于增强miR-181 a-2- 3 p的表达。更重要的是，DNMT 3b和HDAC 2的协同作用抑制了c-Myc在衰老心肌细胞中miR-181 a-2- 3 p启动子处的结合。总之，IPostC通过上调miR-181 a-2- 3 p表达来减轻I/R诱导的老年心肌损伤，这归因于其启动子的转录和表观遗传调控。提示miR-181 a-2- 3 p可能是老年心肌I/R损伤的潜在治疗靶点。
Ischemic postconditioning (IPostC) has been proposed as a strategy to mitigate the risk of ischemia/reperfusion (I/R) injury, and autophagy is involved in I/R-induced aged myocardial injury, while the underlying mechanism of IPostC-regulated autophagy is unknown. Here, we implemented miRNA sequencing analysis in aged cardiomyocytes to identify a novel miR-181a-2-3p after HPostC, which inhibits autophagy by targeting AMBRA1 in aged myocardium to protect I/R-induced aged myocardial injury. Mechanistically, we identified that IPostC can induce DNA hypomethylation and H3K14 hyperacetylation of miR-181a-2-3p promoter due to the decreased binding of DNMT3b and HDAC2 at its promoter, which contributes to enhancing the expression of miR-181a-2-3p. More importantly, cooperation of DNMT3b and HDAC2 inhibits the binding of c-Myc at the miR-181a-2-3p promoter in aged cardiomyocytes. In summary, IPostC attenuates I/R-induced aged myocardial injury through upregulating miR-181a-2-3p expression, which is an attribute to transcriptional and epigenetic regulation of its promoter. Our data indicate that miR-181a-2-3p may be a potential therapeutic target against I/R injury in aged myocardium.
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DOI：
10.1038/s41580-020-0215-2
发表时间：
2020-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baluapuri A;Wolf E;Eilers M
通讯作者：
Eilers M
影响因子：
3.5
作者：
Cho, Young-Dan;Kim, Bong-Su;Ryoo, Hyun-Mo
通讯作者：
Ryoo, Hyun-Mo
糖尿病心肌缺血/再灌注损伤期间，抑制 DNMT-1 通过 NCOA4 介导的铁蛋白自噬减轻铁死亡
影响因子：
7
作者：
Li W;Li W;Wang Y;Leng Y;Xia Z
通讯作者：
Xia Z
影响因子：
5.5
作者：
Chen Y;Fan H;Wang S;Tang G;Zhai C;Shen L
通讯作者：
Shen L
影响因子：
13.3
作者：
Devis-Jauregui L;Eritja N;Davis ML;Matias-Guiu X;Llobet-Navàs D
通讯作者：
Llobet-Navàs D