ArticleThe Journal of biological chemistry2014
Human macrophage SCN5A activates an innate immune signaling pathway for antiviral host defense.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- Computational network analysis of host genetic risk variants of severe COVID-19.Human genomics · 2023Article
- Single coronary artery presenting dilated cardiomyopathy and hyperlipidemia with theFrontiers in cardiovascular medicine · 2023Review
- Innate Immunity in Cardiovascular Diseases-Identification of Novel Molecular Players and Targets.Journal of clinical medicine · 2023Review
- Human macrophages directly modulate iPSC-derived cardiomyocytes at healthy state and congenital arrhythmia model in vitro.Pflugers Archiv : European journal of physiology · 2022Article
- Missense Variant E1295K of Sodium Channel SCN5A Associated With Recurrent Ventricular Fibrillation and Myocardial Inflammation.JACC. Case reports · 2022Article
- Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives.Biomolecules · 2022Review
- Human liver tissue transcriptomics revealed immunometabolic disturbances and related biomarkers in hepatitis B virus-related acute-on-chronic liver failure.Frontiers in microbiology · 2022Article
- In silico drug repurposing in COVID-19: A network-based analysis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Review
- Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers.iScience · 2021Review
- GRP78 modulates cell adhesion markers in prostate Cancer and multiple myeloma cell lines.BMC cancer · 2018Article
- A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced Antiviral State in Dendritic Cells from HIV-1 Elite Controllers.Genome biology · 2018Article
- Module Analysis Captures Pancancer Genetically and Epigenetically Deregulated Cancer Driver Genes for Smoking and Antiviral Response.EBioMedicine · 2018Article
- Gastrointestinal-Renal Axis: Role in the Regulation of Blood Pressure.Journal of the American Heart Association · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pattern recognition receptors contain a binding domain for pathogen-associated molecular patterns coupled to a signaling domain that regulates transcription of host immune response genes. Here, a novel mechanism that links pathogen recognition to channel activation and downstream signaling is proposed. We demonstrate that an intracellular sodium channel variant, human macrophage SCN5A, initiates signaling and transcription through a calcium-dependent isoform of adenylate cyclase, ADCY8, and the transcription factor, ATF2. Pharmacological stimulation with a channel agonist or treatment with cytoplasmic poly(I:C), a mimic of viral dsRNA, activates this pathway to regulate expression of SP100-related genes and interferon β. Electrophysiological analysis reveals that the SCN5A variant mediates nonselective outward currents and a small, but detectable, inward current. Intracellular poly(I:C) markedly augments an inward voltage-sensitive sodium current and inhibits the outward nonselective current. These results suggest human macrophage SCN5A initiates signaling in an innate immune pathway relevant to antiviral host defense. It is postulated that SCN5A is a novel pathogen sensor and that this pathway represents a channel activation-dependent mechanism of transcriptional regulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.