ArticleiScience2024
MicroRNA-452-5p regulates fibrogenesis via targeting TGF-β/SMAD4 axis in SCN5A-knockdown human cardiac fibroblasts.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Therapeutic Lithium Enhances Klotho Expression and Mitochondrial Size and Branching in Human Cardiac Fibroblasts Involving Nuclear Factor-kappa B Inhibition.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Lipid nanoparticle-encapsulated microRNA-192: An anti-inflammatory adjuvant that enhances vaccine efficacy in aged mice.Molecular therapy. Nucleic acids · 2026Article
- Transcriptomic Profiling of MicroRNA and Non-Coding RNA from Whole Blood of African Americans with MASLD.International journal of molecular sciences · 2026Article
- MicroRNA-143-3p and miR-452-5p: A Fingerprint for the Diagnosis of Aortic Stenosis in the Geriatric Population.Biomedicines · 2025Article
- The pivotal role of TGF-β/Smad pathway in fibrosis pathogenesis and treatment.Frontiers in oncology · 2025Review
- Protocol for adeno-associated virus-mediated miRNA delivery in a rat heart failure model.STAR protocols · 2024Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mutated SCN5A gene encoding defective Nav1.5 protein causes arrhythmic ailments and is associated with enhanced cardiac fibrosis. This study investigated whether SCN5A mutation directly affects cardiac fibroblasts and explored how defective SCN5A relates to cardiac fibrosis. SCN5A knockdown (SCN5AKD) human cardiac fibroblasts (HCF) had higher collagen, α-SMA, and fibronectin expressions. Micro-RNA deep sequencing and qPCR analysis revealed the downregulation of miR-452-5p and bioinformatic analysis divulged maladaptive upregulation of transforming growth factor β (TGF-β) signaling in SCN5AKD HCF. Luciferase reporter assays validated miR-452-5p targets SMAD4 in SCN5AKD HCF. Moreover, miR-452-5p mimic transfection in SCN5AKD HCF or AAV9-mediated miR-452-5p delivery in isoproterenol-induced heart failure (HF) rats, resulted in the attenuation of TGF-β signaling and fibrogenesis. The exogenous miR-452-5p significantly improved the poor cardiac function in HF rats. In conclusion, miR-452-5p regulates cardiac fibrosis progression by targeting the TGF-β/SMAD4 axis under the loss of the SCN5A gene.
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Registered trials
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