ArticleJournal of the American Society of Nephrology : JASN2014
Genetic susceptibility and loss of Nr4a1 enhances macrophage-mediated renal injury in CKD.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Identification of Ferroptosis-Related Hub Genes and Immune Infiltration Landscape in Chronic Kidney Disease via Bioinformatics and Experimental Verification.Immunity, inflammation and disease · 2026Article
- Macrophage Niche Reconstitution Reveals Dynamic Transcriptional and Communication Networks Renal Macrophage-Epithelial Communication.Research square · 2026Article
- Bruceine A protects nuclear receptor 4A1 from ubiquitin-degradation to alleviate mesangial proliferative glomerulonephritis.Signal transduction and targeted therapy · 2025Article
- PPARG-centered regulatory network of ferroptosis in lupus nephritis: insights by integrated comprehensive bioinformatics analysis and machine learning.Clinical rheumatology · 2025Article
- Review
- Identify the co-expressed genes of hypertensive nephropathy and diabetic nephropathy.Scientific reports · 2025Article
- Development and Validation of a Diagnostic Model for AKI Based on the Analysis of Ferroptosis-related Genes.Current medicinal chemistry · 2025Article
- SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1.Molecular medicine (Cambridge, Mass.) · 2024Article
- CHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy.Communications biology · 2024Article
- Nuclear receptor 4A1 ameliorates UUO-induced renal fibrosis by inhibiting the PI3K/AKT pathway.Scientific reports · 2024Article
- Article
- Single-nuclei transcriptome analysis of channel catfish spleen provides insight into the immunome of an aquaculture-relevant species.PloS one · 2024Article
- Identification of biomarkers for the diagnosis of chronic kidney disease (CKD) with non-alcoholic fatty liver disease (NAFLD) by bioinformatics analysis and machine learning.Frontiers in endocrinology · 2023Article
- Renal tubular gen e biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis.Renal failure · 2022Article
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- Role of NR4A family members in myeloid cells and leukemia.Current research in immunology · 2022Article
- Nephron-deficient HSRA rats exhibit renal injury with age but have limited renal damage from streptozotocin-induced hyperglycemia.American journal of physiology. Renal physiology · 2021Article
- Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.Scientific reports · 2021Article
- JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2.Frontiers in medicine · 2021Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Nuclear hormone receptors of the NR4A subgroup have been implicated in cancer, atherosclerosis, and metabolic disease. However, little is known about the role of these receptors in kidney health or disease. Nr4a1-deficient rats (Nr4a1(-/-)) developed on a genetic background susceptible to kidney injury (fawn-hooded hypertensive rat [FHH]) were evaluated for BP, proteinuria, renal function, and metabolic parameters from 4 to 24 weeks-of-age. By week 24, Nr4a1(-/-) rats exhibited significantly higher proteinuria (approximately 4-fold) and decreased GFR compared with FHH controls. The severity of tubular atrophy, tubular casts, and interstitial fibrosis increased significantly in Nr4a1(-/-) rats and was accompanied by a large increase in immune cell infiltration, predominantly macrophages and to a lesser extent T cells and B cells. Global transcriptome and network analyses at weeks 8, 16, and 24 identified several proinflammatory genes and pathways differentially regulated between strains. Bone marrow crosstransplantation studies demonstrated that kidney injury in Nr4a1(-/-) rats was almost completely rescued by bone marrow transplanted from FHH controls. In vitro, macrophages isolated from Nr4a1(-/-) rats demonstrated increased immune activation compared with FHH-derived macrophages. In summary, the loss of Nr4a1 in immune cells appears to cause the increased kidney injury and reduced renal function observed in the Nr4a1(-/-) model.
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