Department of Cardiology, The Third Affiliated Hospital of Nanchang University (The First Hospital of Nanchang), Nanchang, Jiangxi, China.
Department of Pediatrics, XD Group Hospital, Xi'an, Shaanxi, China.
Immun Inflamm Dis. 2021 Mar;9(1):288-298. doi: 10.1002/iid3.392. Epub 2020 Dec 17.
Emerging articles have profiled the relations between microRNAs and viral myocarditis. This research was unearthed to explore the capacity of miR-425-3p on cardiomyocyte apoptosis in mice with viral myocarditis and its mechanism.
A total of 120 mice were classified into 4 groups in a random fashion (n = 30). The mice were intraperitoneally injected with coxsackievirus type B3 (CVB3) to induce myocarditis. On the 7th day after CVB3 infection, 10 mice in each group were euthanized to assess the heart function indices of mice, observe the pathological conditions, detect myocardial tissue apoptosis, and measure the inflammatory factor levels in myocardial tissues. Expression of miR-425-3p, transforming growth factor (TGF-β1), and apoptosis-associated proteins in myocardial tissues was determined. The remaining 20 mice in each group were used for survival observation. The luciferase activity assay was implemented to validate the relationship between miR-425-3p and TGF-β1. miR-425-3p mimic was transfected into mouse cardiomyocytes HL-1 and then infected with CVB3 to further verify the regulatory effect of miR-425-3p on the cardiomyocyte apoptosis in viral myocarditis.
miR-425-3p was lowly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR-425-3p improved the cardiac function, alleviated pathological conditions, reduced cardiomyocyte apoptosis, decreased Bax and cleaved Caspase-3 expression, elevated Bcl-2 expression, decreased levels of inflammatory factors and improved survival rate of mice with viral myocarditis. Luciferase activity assay verified that miR-425-3p could bind to TGF-β1, and overexpressed miR-425-3p suppressed TGF-β1, p-smad2/smad2 and p-smad3/smad3 expression. In vitro experiments further verified that overexpression of miR-425-3p inhibited the apoptosis of CVB3-HL-1 cells, and the addition of TGF-β1 would reverse this effect.
Our research indicates that miR-425-3p is poorly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR-425-3p inhibits cardiomyocyte apoptosis and myocardial inflammation in mice with viral myocarditis as well as improves their survival rates through suppressing the TGF-β1/smad axis.
新出现的文章描述了 microRNAs 与病毒性心肌炎之间的关系。本研究旨在探讨 miR-425-3p 对病毒性心肌炎小鼠心肌细胞凋亡的影响及其机制。
将 120 只小鼠随机分为 4 组（n = 30）。采用柯萨奇病毒 B3（CVB3）腹腔注射法诱导心肌炎。在 CVB3 感染后第 7 天，每组处死 10 只小鼠，评估小鼠心功能指标，观察病理情况，检测心肌组织细胞凋亡情况，测量心肌组织中炎症因子水平。检测心肌组织中 miR-425-3p、转化生长因子（TGF-β1）和凋亡相关蛋白的表达。每组剩余 20 只小鼠用于生存观察。采用荧光素酶活性检测验证 miR-425-3p 与 TGF-β1 的关系。转染 miR-425-3p 模拟物至 HL-1 心肌细胞，然后感染 CVB3，进一步验证 miR-425-3p 对病毒性心肌炎中心肌细胞凋亡的调控作用。
病毒性心肌炎小鼠心肌组织中 miR-425-3p 表达水平降低。过表达 miR-425-3p 可改善心脏功能，减轻病理损伤，减少心肌细胞凋亡，降低 Bax 和 cleaved Caspase-3 表达，升高 Bcl-2 表达，降低炎症因子水平，提高病毒性心肌炎小鼠的生存率。荧光素酶活性检测验证 miR-425-3p 可与 TGF-β1 结合，过表达 miR-425-3p 可抑制 TGF-β1、p-smad2/smad2 和 p-smad3/smad3 的表达。体外实验进一步验证，过表达 miR-425-3p 可抑制 CVB3-HL-1 细胞凋亡，而加入 TGF-β1 可逆转这一作用。
本研究表明，病毒性心肌炎小鼠心肌组织中 miR-425-3p 表达降低。过表达 miR-425-3p 可通过抑制 TGF-β1/smad 轴抑制病毒性心肌炎小鼠心肌细胞凋亡和心肌炎症，提高其生存率。
