ArticleThe Journal of biological chemistry2014
A20 regulates atherogenic interferon (IFN)-γ signaling in vascular cells by modulating basal IFNβ levels.
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 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- A20 Inhibits IFN-γ Signaling in Hepatocellular Carcinoma Cells by Binding to STAT1, Compromising Anti-Tumor Immunity.Cancer science · 2026Article
- How I Treat: Haploinsufficiency of A20.Journal of human immunity · 2026Review
- Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease.Annals of vascular surgery · 2024Review
- A20 in Kidney Transplantation and Autoimmunity.International journal of molecular sciences · 2024Review
- Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRβ.Frontiers of medicine · 2024Article
- LINC01686 affects LPS-induced cytokine expression via the miR-18a-5p/A20/STAT1 axis in THP-1 cells.Immunity, inflammation and disease · 2024Article
- The Complexity of Being A20: From Biological Functions to Genetic Associations.Journal of clinical immunology · 2024Review
- Associations of carotid intima media thickness with gene expression in whole blood and genetically predicted gene expression across 48 tissues.Human molecular genetics · 2022Article
- Identification of a Novel Mutation inFrontiers in immunology · 2022Article
- Knockdown of long noncoding RNA GAS5 reduces vascular smooth muscle cell apoptosis by inactivating EZH2-mediated RIG-I signaling pathway in abdominal aortic aneurysm.Journal of translational medicine · 2021Article
- Down-regulation of A20 promotes immune escape of lung adenocarcinomas.Science translational medicine · 2021Article
- UFMylation inhibits the proinflammatory capacity of interferon-γ-activated macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A20/TNFAIP3 Increases ENOS Expression in an ERK5/KLF2-Dependent Manner to Support Endothelial Cell Health in the Face of Inflammation.Frontiers in cardiovascular medicine · 2021Article
- Phenotypic characteristics of commonly used inbred mouse strains.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.The journal of pathology. Clinical research · 2020Article
- Downregulation of A20 increases the cytotoxicity of IFN-γ in hepatocellular carcinoma cells.Drug design, development and therapy · 2017Article
- A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular Allografts: Implications for Clinical Transplantation.Transplantation · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
IFNγ signaling in endothelial (EC) and smooth muscle cells (SMC) is a key culprit of pathologic vascular remodeling. The impact of NF-κB inhibitory protein A20 on IFNγ signaling in vascular cells remains unknown. In gain- and loss-of-function studies, A20 inversely regulated expression of IFNγ-induced atherogenic genes in human EC and SMC by modulating STAT1 transcription. In vivo, inadequate A20 expression in A20 heterozygote mice aggravated intimal hyperplasia following partial carotid artery ligation. This outcome uniquely associated with increased levels of Stat1 and super-induction of Ifnγ-dependent genes. Transcriptome analysis of the aortic media from A20 heterozygote versus wild-type mice revealed increased basal Ifnβ signaling as the likely cause for higher Stat1 transcription. We confirmed higher basal IFNβ levels in A20-silenced human SMC and showed that neutralization or knockdown of IFNβ abrogates heightened STAT1 levels in these cells. Upstream of IFNβ, A20-silenced EC and SMC demonstrated higher levels of phosphorylated/activated TANK-binding kinase-1 (TBK1), a regulator of IFNβ transcription. This suggested that A20 knockdown increased STAT1 transcription by enhancing TBK1 activation and subsequently basal IFNβ levels. Altogether, these results uncover A20 as a key physiologic regulator of atherogenic IFNγ/STAT1 signaling. This novel function of A20 added to its ability to inhibit nuclear factor-κB (NF-κB) activation solidifies its promise as an ideal therapeutic candidate for treatment and prevention of vascular diseases. In light of recently discovered A20/TNFAIP3 (TNFα-induced protein 3) single nucleotide polymorphisms that impart lower A20 expression or function, these results also qualify A20 as a reliable clinical biomarker for vascular risk assessment.
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