ArticleAmerican journal of respiratory cell and molecular biology2014
Nur77 suppresses pulmonary artery smooth muscle cell proliferation through inhibition of the STAT3/Pim-1/NFAT pathway.
Article in American journal of respiratory cell and molecular biology, 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, 41 citations in OpenAlex.
- The critical role of NFAT transcription factors in pulmonary arterial remodeling and pulmonary hypertension: from PASMC proliferation to therapeutic targeting.Molecular biology reports · 2026Review
- Bruceine A protects nuclear receptor 4A1 from ubiquitin-degradation to alleviate mesangial proliferative glomerulonephritis.Signal transduction and targeted therapy · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension by downregulating TGF-β1-Smad2/3 pathway.BMC cardiovascular disorders · 2024Article
- Article
- Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.Signal transduction and targeted therapy · 2023Review
- A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.Nature cell biology · 2023Article
- HDAC1 disrupts the tricarboxylic acid (TCA) cycle through the deacetylation of Nur77 and promotes inflammation in ischemia-reperfusion mice.Cell death discovery · 2023Article
- Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues.Cells · 2019Review
- Chronic Intermittent Ethanol Exposure Induces Upregulation of Matrix Metalloproteinase-9 in the Rat Medial Prefrontal Cortex and Hippocampus.Neurochemical research · 2019Article
- Key Functions and Therapeutic Prospects of Nur77 in Inflammation Related Lung DiseasesThe American journal of pathology · 2019Review
- The role of nuclear factor of activated T cells in pulmonary arterial hypertension.Cell cycle (Georgetown, Tex.) · 2017Review
- Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation.Biochemical pharmacology · 2014Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The orphan nuclear receptor 4A (NR4A) family plays critical roles in the regulation of cell proliferation, differentiation, and survival in the cardiovascular system. However, the molecular mechanisms underlying the regulation of NR4A receptor expression and its role in pulmonary artery smooth muscle cell (PASMC) function remain unclear. Here, we investigated whether the NR4A family regulates PASMC proliferation, and if so, which mechanisms are involved. By using quantitative real-time RT-PCR, we showed that the orphan nuclear receptor Nur77 was the most abundant member of NR4A family expressed in rat PASMCs, as compared with the two other members, NOR-1 and Nurr1. In rat PASMCs, expression of Nur77 was robustly induced in response to several pathologic stimuli of pulmonary arterial hypertension (PAH), such as hypoxia, 5-hydroxytryptamine (5-HT), platelet-derived growth factor, and endothelin-1. Importantly, Nur77 was also significantly increased in lungs of rats with monocrotaline-induced PAH. Furthermore, we demonstrated that 5-HT markedly up-regulated Nur77 expression through the mitogen-activated protein kinases/extracellular signal-regulated kinase 1/2 pathway. Overexpression of Nur77 inhibited 5-HT-induced PASMC proliferation, as well as the expression of cyclin D1 and proliferating cell nuclear antigen. Mechanistically, we demonstrated that Nur77 specifically interacts with signal transducer and activator of transcription 3, thus inhibiting its phosphorylation and expression of its target genes, such as Pim-1, nuclear factor of activated T cells c2, and survivin in PASMCs. These results indicate that Nur77 is a novel negative-feedback regulator of PASMC proliferation through inhibition of the signal transducer and activator of transcription 3/Pim-1/nuclear factor of activated T cells axis. Modulation of Nur77 activity may potentially represent a novel therapeutic strategy for the treatment of PAH.
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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.