Zhou Shan, Zhang Li, Duan Xiuyun, Liu Keyu, Yingnan You, Ma Mengjie, Han Bo
Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Front Cell Dev Biol. 2025 May 13;13:1600103. doi: 10.3389/fcell.2025.1600103. eCollection 2025.
Our Previous research revealed significant differences in exosome-mediated intercellular miR-425a-5p between normal children and those with fulminant myocarditis. We sought to elucidate the molecular underpinnings and functional implications of miR-425a-5p in the context of myocarditis progression.
Bioinformatics techniques were employed to predict NRAS as the target gene of miR-425a-5p. We constructed a cellular myocarditis paradigm through LPS-mediated provocation of AC16 cardiomyocyte cultures. MiR-425a-5p was overexpressed, and the expressions of NRAS, cell apoptosis, and proinflammatory cytokine profiles, encompassing IL-1β, IL-6, and TNF-α, were comprehensively quantified. An experimental autoimmune myocarditis (EAM) mouse model was created using adeno-associated virus (AAV) for miR-425a-5p overexpression. Comprehensive histopathological analyses were conducted utilizing multiple staining techniques, including hematoxylin-eosin (HE), immunohistochemical, and Masson trichrome methodologies to characterize tissue responses.
The study demonstrated that miR-425a-5p alleviated the inflammatory response in both AC16 cells and EAM mice through NRAS mediation. Single-cell data analysis of cardiac immune cells revealed that miR-425a-5p promoted Treg cell differentiation and improved cardiac function.
MiR-425a-5p plays a crucial role in modulating inflammatory responses in myocarditis, potentially offering a novel therapeutic strategy for managing the disease.
我们之前的研究揭示了正常儿童与暴发性心肌炎患儿之间，外泌体介导的细胞间miR-425a-5p存在显著差异。我们试图阐明miR-425a-5p在心肌炎进展过程中的分子基础和功能意义。
采用生物信息学技术预测NRAS为miR-425a-5p的靶基因。我们通过脂多糖介导刺激AC16心肌细胞培养构建了细胞心肌炎模型。过表达miR-425a-5p，并全面定量NRAS、细胞凋亡以及包括IL-1β、IL-6和TNF-α在内的促炎细胞因子谱的表达。使用腺相关病毒（AAV）构建用于过表达miR-425a-5p的实验性自身免疫性心肌炎（EAM）小鼠模型。利用苏木精-伊红（HE）、免疫组织化学和Masson三色染色等多种染色技术进行全面的组织病理学分析，以表征组织反应。
研究表明，miR-425a-5p通过NRAS介导减轻了AC16细胞和EAM小鼠的炎症反应。对心脏免疫细胞的单细胞数据分析显示，miR-425a-5p促进了调节性T细胞（Treg）分化并改善了心脏功能。
miR-425a-5p在调节心肌炎炎症反应中起关键作用，可能为该疾病的治疗提供一种新的治疗策略。
