AUTHOR=Zhou Shan , Zhang Li , Duan Xiuyun , Liu Keyu , Yingnan You , Ma Mengjie , Han Bo 

TITLE=MiR-425-5p intervenes in autoimmune myocarditis by regulating Treg cell differentiation through NRAS

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1600103

DOI=10.3389/fcell.2025.1600103

ISSN=2296-634X

ABSTRACT=AimOur 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.MethodsBioinformatics 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.ResultsThe 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.ConclusionMiR-425a-5p plays a crucial role in modulating inflammatory responses in myocarditis, potentially offering a novel therapeutic strategy for managing the disease.