ArticleAmerican journal of physiology. Renal physiology2019
Blockade of enhancer of zeste homolog 2 alleviates renal injury associated with hyperuricemia.
Article in American journal of physiology. Renal physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 52 citations in OpenAlex.
- Genetic depletion or pharmacological degradation of EZH2 attenuates renal fibrosis via suppressing Notch signaling.Clinical epigenetics · 2025Article
- Histone methylation of kidney disease: fact or fantasy?Renal failure · 2025Review
- Epigenetic histone modifications in kidney disease and epigenetic memory.Clinical and experimental nephrology · 2025Review
- EZH2 as a major histone methyltransferase in PDGF-BB-activated orbital fibroblast in the pathogenesis of Graves' ophthalmopathy.Scientific reports · 2024Article
- Article
- The disruptor of telomeric silencing 1-like (DOT1L) promotes peritoneal fibrosis through the upregulation and activation of protein tyrosine kinases.Molecular biomedicine · 2024Article
- Correlation Between Uric Acid/High Density Lipoprotein Cholesterol Ratio and Postoperative AKI in Patients with CABG.International journal of general medicine · 2024Article
- Enhancer of zeste homolog 2 promotes renal fibrosis after acute kidney injury by inducing epithelial-mesenchymal transition and activation of M2 macrophage polarization.Cell death & disease · 2023Article
- Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023Review
- Drp1 activates ROS/HIF-1α/EZH2 and triggers mitochondrial fragmentation to deteriorate hypercalcemia-associated neuronal injury in mouse model of chronic kidney disease.Journal of neuroinflammation · 2022Article
- The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases.Frontiers in pharmacology · 2022Review
- The Role of Histone H3 Methylation in Acute Kidney Injury.Drug design, development and therapy · 2022Review
- Protein Methylation in Diabetic Kidney Disease.Frontiers in medicine · 2022Review
- Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway.Molecular medicine reports · 2021Article
- Silencing of O-linked N-acetylglucosamine transferase ameliorates hypercalcemia-induced neurotoxicity in renal failure by regulating EZH2/KLF2/CXCL1 axis.Cell death & disease · 2021Article
- Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases.Frontiers in physiology · 2021Review
- Zishen Qingre Tongluo Formula Improves Renal Fatty Acid Oxidation and Alleviated Fibrosis via the Regulation of the TGF-BioMed research international · 2021Article
- Research Advances in the Mechanisms of Hyperuricemia-Induced Renal Injury.BioMed research international · 2020Review
- Histone Methyltransferases as Therapeutic Targets for Kidney Diseases.Frontiers in pharmacology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Hyperuricemia has been identified as an independent risk factor for chronic kidney disease (CKD) and is associated with the progression of kidney diseases. It remains unknown whether enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, can regulate metabolism of serum uric acid and progression of renal injury induced by hyperuricemia. In this study, we demonstrated that blockade of EZH2 with 3-DZNeP, a selective EZH2 inhibitor, or silencing of EZH2 with siRNA inhibited uric acid-induced renal fibroblast activation and phosphorylation of Smad3, epidermal growth factor receptor (EGFR), and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured renal fibroblasts. Inhibition of EZH2 also suppressed proliferation of renal fibroblasts and epithelial-mesenchymal transition of tubular cells. In a mouse model of renal injury induced by hyperuricemia, EZH2 and trimethylation of histone H3 at lysine27 expression levels were enhanced, which was coincident with renal damage and increased expression of lipocalin-2 and cleaved caspase-3. Inhibition of EZH2 with 3-DZNeP blocked all these responses. Furthermore, 3-DZNeP treatment decreased the level of serum uric acid and xanthine oxidase activity, alleviated renal interstitial fibrosis, inhibited activation of transforming growth factor-β/Smad3, EGFR/ERK1/2, and nuclear factor-κB signaling pathways, as well as reduced expression of multiple chemokines/cytokines. Collectively, EZH2 inhibition can reduce the level of serum uric acid and alleviate renal injury and fibrosis through a mechanism associated with inhibition of multiple signaling pathways. Targeting EZH2 may be a novel strategy for the treatment of hyperuricemia-induced CKD.
Indexed as
Identifiers
What OpenQuestion holds
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.