Department of Cardiovascular Surgery, PLA General Hospital, No. 28. Fuxing Road, Haidian District, Beijing, 100853, China.
Department of Cardiovascular Surgery, PLA General Hospital, No. 28. Fuxing Road, Haidian District, Beijing, 100853, China.
Mol Immunol. 2021 Feb;130:96-103. doi: 10.1016/j.molimm.2020.11.009. Epub 2020 Dec 5.
At present, studies have focused on microRNAs (miRNAs) in myocardial ischemia-reperfusion injury (MI/RI). But the specific role of miR-30e hasn't been fully explored. Thus, this study is to uncover the mechanism of miR-30e in MI/RI.
MI/RI models of rats and hypoxia/reoxygenation injury (H/R) models of H9C2 cardiomyocytes were established. Rats were injected with miR-30e and SRY-related high mobility group-box gene 9 (SOX9)-related oligonucleotides or vectors to explore their roles in MI/RI. H9C2 cardiomyocytes were transfected with restored miR-30e and depleted SOX9 to decipher their function in H/R injury. miR-30e and SOX9 expression in myocardial tissues and cardiomyocytes were detected. Online website prediction and luciferase activity assay were applied to validate the targeting relationship between miR-30e and SOX9.
Decreased miR-30e and increased SOX9 were found in myocardial tissues of MI/RI rats and H/R-treated cardiomyocytes. miR-30e targeted SOX9. miR-30e up-regulation or SOX9 down-regulation reduced cardiac function damage and suppressed oxidative stress, inflammation, cardiomyocyte apoptosis and myocardial enzymes in myocardial tissues of MI/RI rats. Restoring miR-30e or silencing SOX9 energized cell viability and inhibited apoptosis of H/R-treated cardiomyocytes. Down-regulating SOX9 reversed the effects of miR-30e down-regulation on myocardial injury, ventricular remodeling, cardiomyocyte damage and apoptosis in MI/RI.
It is concluded that miR-30e elevation alleviated cardiac function damage and promoted ventricular remodeling via SOX9 repression.
目前，研究集中在心肌缺血再灌注损伤（MI/RI）中的 microRNAs（miRNAs）。但是 miR-30e 的具体作用尚未充分探索。因此，本研究旨在揭示 miR-30e 在 MI/RI 中的作用机制。
建立大鼠 MI/RI 模型和 H9C2 心肌细胞缺氧/复氧损伤（H/R）模型。通过注射 miR-30e 和 SOX9 相关寡核苷酸或载体来研究它们在 MI/RI 中的作用。用恢复的 miR-30e 和耗尽的 SOX9 转染 H9C2 心肌细胞，以阐明它们在 H/R 损伤中的功能。检测心肌组织和心肌细胞中 miR-30e 和 SOX9 的表达。在线网站预测和荧光素酶活性测定用于验证 miR-30e 和 SOX9 之间的靶向关系。
在 MI/RI 大鼠的心肌组织和 H/R 处理的心肌细胞中发现 miR-30e 减少和 SOX9 增加。miR-30e 靶向 SOX9。上调 miR-30e 或下调 SOX9 可减轻 MI/RI 大鼠心肌组织的心脏功能损伤，并抑制氧化应激、炎症、心肌细胞凋亡和心肌酶。恢复 miR-30e 或沉默 SOX9 可增强 H/R 处理的心肌细胞的活力并抑制其凋亡。下调 SOX9 可逆转 miR-30e 下调对 MI/RI 中心肌损伤、心室重构、心肌细胞损伤和凋亡的作用。
miR-30e 的上调通过抑制 SOX9 缓解心脏功能损伤并促进心室重构。
