Hubei Province Key Laboratory of Occupational Hazard Identification and Control, College of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, Hubei, People's Republic of China.
Cell Mol Biol Lett. 2024 Apr 20;29(1):55. doi: 10.1186/s11658-024-00576-8.
Viral myocarditis (VMC) is a disease resulting from viral infection, which manifests as inflammation of myocardial cells. Until now, the treatment of VMC is still a great challenge for clinicians. Increasing studies indicate the participation of miR-29b-3p in various diseases. According to the transcriptome sequencing analysis, miR-29b-3p was markedly upregulated in the viral myocarditis model. The purpose of this study was to investigate the role of miR-29b-3p in the progression of VMC.
We used CVB3 to induce primary cardiomyocytes and mice to establish a model of viral myocarditis. The purity of primary cardiomyocytes was identified by immunofluorescence. The cardiac function of mice was detected by Vevo770 imaging system. The area of inflammatory infiltration in heart tissue was shown by hematoxylin and eosin (H&E) staining. The expression of miR-29b-3p and DNMT3A was detected by quantitative real time polymerase chain reaction (qRT-PCR). The expression of a series of pyroptosis-related proteins was detected by western blot. The role of miR-29b-3p/DNMT3A in CVB3-induced pyroptosis of cardiomyocytes was studied in this research.
Our data showed that the expression of miR-29b-3p was upregulated in CVB3-induced cardiomyocytes and heart tissues in mice. To explore the function of miR-29b-3p in CVB3-induced VMC, we conducted in vivo experiments by knocking down the expression of miR-29b-3p using antagomir. We then assessed the effects on mice body weight, histopathology changes, myocardial function, and cell pyroptosis in heart tissues. Additionally, we performed gain/loss-of-function experiments in vitro to measure the levels of pyroptosis in primary cardiomyocytes. Through bioinformatic analysis, we identified DNA methyltransferases 3A (DNMT3A) as a potential target gene of miR-29b-3p. Furthermore, we found that the expression of DNMT3A can be modulated by miR-29b-3p during CVB3 infection.
Our results demonstrate a correlation between the expression of DNMT3A and CVB3-induced pyroptosis in cardiomyocytes. These findings unveil a previously unidentified mechanism by which CVB3 induces cardiac injury through the regulation of miR-29b-3p/DNMT3A-mediated pyroptosis.
病毒性心肌炎（VMC）是一种由病毒感染引起的疾病，表现为心肌细胞炎症。到目前为止，VMC 的治疗仍然是临床医生面临的一大挑战。越来越多的研究表明 miR-29b-3p 参与了各种疾病的发生。根据转录组测序分析，miR-29b-3p 在病毒性心肌炎模型中显著上调。本研究旨在探讨 miR-29b-3p 在 VMC 进展中的作用。
我们使用 CVB3 诱导原代心肌细胞和小鼠建立病毒性心肌炎模型。通过免疫荧光鉴定原代心肌细胞的纯度。使用 Vevo770 成像系统检测小鼠心功能。苏木精和伊红（H&E）染色显示心脏组织中炎症浸润面积。定量实时聚合酶链反应（qRT-PCR）检测 miR-29b-3p 和 DNMT3A 的表达。Western blot 检测一系列细胞焦亡相关蛋白的表达。本研究研究了 miR-29b-3p/DNMT3A 在 CVB3 诱导的心肌细胞焦亡中的作用。
我们的数据显示，miR-29b-3p 在 CVB3 诱导的心肌细胞和小鼠心脏组织中表达上调。为了探讨 miR-29b-3p 在 CVB3 诱导的 VMC 中的功能，我们使用 antagomir 下调 miR-29b-3p 的表达进行体内实验。然后评估其对小鼠体重、组织病理学变化、心肌功能和心脏组织细胞焦亡的影响。此外，我们还进行了体外的增益/缺失功能实验，以测量原代心肌细胞的焦亡水平。通过生物信息学分析，我们确定 DNA 甲基转移酶 3A（DNMT3A）是 miR-29b-3p 的潜在靶基因。此外，我们发现 DNMT3A 的表达可受 CVB3 感染时 miR-29b-3p 的调节。
我们的结果表明，DNMT3A 的表达与 CVB3 诱导的心肌细胞焦亡之间存在相关性。这些发现揭示了 CVB3 通过调节 miR-29b-3p/DNMT3A 介导的细胞焦亡诱导心脏损伤的一种新的未知机制。
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