Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cell Infect Microbiol. 2021 Aug 24;11:704919. doi: 10.3389/fcimb.2021.704919. eCollection 2021.
Long non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.
FM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.
First, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.
Expression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.
长链非编码 RNA(lncRNA)是病毒感染和炎症反应的关键调节因子。然而,lncRNA 在急性心肌炎(AM),尤其是暴发性心肌炎(FM)中的作用尚不清楚。
采用柯萨奇 B3 病毒(CVB3)在不同小鼠品系中诱导 FM 和非暴发性心肌炎(NFM)。然后,通过测序检测心脏组织中 lncRNA 的表达谱。最后,通过 Pearson/Spearman 秩相关、京都基因与基因组百科全书(KEGG)和 Cytoscape 3.7 分析模式。
首先,在 CVB3 处理的 A/J、C57BL/6、BALB/c 和 C3H 小鼠心肌炎中,分别鉴定出 1216、983、1606 和 2459 个差异表达的 lncRNA。其中,88 个 lncRNA 在所有四个模型中均存在差异表达。实时定量聚合酶链反应分析进一步证实,在所有四个模型中,前六个共同失调的 lncRNA 中有四个上调。此外,ENSMUST00000188819、ENSMUST00000199139 和 ENSMUST00000222401 的水平在心脏和脾脏中显著升高,与心脏炎症浸润的严重程度相关。同时,检测到 923 个 FM 特异性失调的 lncRNA,其中 MSTRG.26098.49、MSTRG.31307.11、MSTRG.31357.2 和 MSTRG.32881.28 的水平与 LVEF 高度相关。
lncRNA 在急性心肌炎中表达明显失调,可能在 AM 的进展中发挥不同的作用。