ArticleCell death discovery2018
NR4A2 protects cardiomyocytes against myocardial infarction injury by promoting autophagy.
Article in Cell death discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- The Cavβ4 subunit of Cav1.2 channels antagonizes isoproterenol-induced hypertrophy in rat cardiac muscle cells by down-regulating miR-183-5p.Physiological reports · 2026Article
- NR4A2-driven metabolic reprogramming in the heart: from adaptive response to maladaptive remodeling.Physiological genomics · 2026Article
- Article
- Review
- Dual Targeting of Orphan Nuclear Receptors NR4A1 and NR4A2 for Nonhormonal Endometriosis Therapy.Endocrinology · 2025Article
- Dysregulation of Serum miR-212-3p Serves as a Biomarker to Predict Disease Onset and Short-Term Prognosis in Acute Coronary Syndrome Patients.Anatolian journal of cardiology · 2025Article
- Comprehensive Analysis of N6-Methyladenosine Methylation in Transverse Aortic Constriction-Induced Cardiac Fibrosis Based on MeRIP-Seq Analysis.Biomedicines · 2025Article
- Hypoxia-associated genes and metabolic abnormalities in peripheral blood mononuclear cells of type 1 diabetes mellitus patients.Hereditas · 2025Article
- NR4A2 attenuates early brain injury after intracerebral hemorrhage by promoting M2 microglial polarization via TLR4/TRAF6/NF-κB pathway inhibition.Cellular and molecular life sciences : CMLS · 2025Article
- Luteolin ameliorates rat model of metabolic syndrome-induced cardiac injury by apoptosis suppression and autophagy promotion via NR4A2/p53 regulation.BMC complementary medicine and therapies · 2025Article
- Review
- Cytokine Adsorption During Ex Vivo Blood Perfusion Improves Contractility of Donation After Circulatory Death Hearts.Journal of the American Heart Association · 2024Article
- The Potential Contribution of MyomiRs miR-133a-3p, -133b, and -206 Dysregulation in Cardiovascular Disease Risk.International journal of molecular sciences · 2024Article
- Early Injury Landscape in Vein Harvest by Single-Cell and Spatial Transcriptomics.Circulation research · 2024Article
- Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia-Reperfusion Injury through NR4A2-Mediated Mitophagy.International journal of molecular sciences · 2024Article
- Integrated single-nuclei and spatial transcriptomic analysis reveals propagation of early acute vein harvest and distension injury signaling pathways following arterial implantation.bioRxiv : the preprint server for biology · 2024Article
- Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging.Journal of nanobiotechnology · 2024Article
- A role of NR4A2 in Graves' disease: regulation of Th17/Treg.Endocrine · 2024Article
- Differential expression and significance of peripheral blood genes in coronary artery heart disease.Journal of thoracic disease · 2022Article
- JNK-dependent phosphorylation and nuclear translocation of EGR-1 promotes cardiomyocyte apoptosis.Apoptosis : an international journal on programmed cell death · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myocardial infarction (MI), characterized by ischemia-induced cardiomyocyte apoptosis, is the leading cause of mortality worldwide. NR4A2, a member of the NR4A orphan nucleus receptor family, is upregulated in mouse hearts with MI injury. Furthermore, NR4A2 knockdown aggravates heart injury as evidenced by enlarged hearts and increased apoptosis. To elucidate the underlying mechanisms of NR4A2-regulated apoptosis, we used H9c2 cardiomyocytes deprived of serum and neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia to mimic ischemic conditions in vivo. As NR4A2 knockdown aggravates cardiomyocyte apoptosis, while NR4A2 overexpression ameliorates it, NR4A2 upregulation was considered an adaptive response to ischemia-induced cardiomyocyte apoptosis. By detecting changes in LC3 and using autophagy detection tools including Bafilomycin A1, 3MA and rapamycin, we found that NR4A2 knockdown promoted apoptosis through blocking autophagic flux. This apoptotic response was phenocopied by downregulation of NR4A2 after autophagic flux was impaired by Bafilomycin A1. Further study showed that NR4A2 binds to p53 directly and decreases its levels when it inhibits apoptosis; thus, p53/Bax is the downstream effector of NR4A2-mediated apoptosis, as previously reported. Changes in p53/Bax that were regulated by NR4A2 were also detected in injured hearts with NR4A2 knockdown. In addition, miR-212-3p is the upstream regulator of NR4A2, and it could downregulate the expression of NR4A2, as well as p53/Bax. The mechanism underlying the role of NR4A2 in apoptosis and autophagy was elucidated, and NR4A2 may be a therapeutic drug target for heart failure.
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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.