ArticleCell death & disease2018
Targeting enhancer of zeste homolog 2 protects against acute kidney injury.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Epigenetically silencing gluconeogenic enzyme PCK1 by EZH2 promotes renal tubulointerstitial fibrosis.Molecular biomedicine · 2026Article
- Article
- Long non-coding RNA STMN1P2 promotes breast cancer doxorubicin resistance by inhibiting pyroptosis through the hnRNPU-EZH2-TARF6-MALT1-caspase-1 pathway.Acta pharmacologica Sinica · 2026Article
- Histone methylation of kidney disease: fact or fantasy?Renal failure · 2025Review
- Cellular senescence in kidney diseases.Chinese medical journal · 2025Review
- Tri-domain proteins 27 alleviates ischemia-reperfusion injury-induced acute kidney injury by promoting Gli-like transcription factor 1 expression via the inhibition of polycomb repressive complex 2 activity.Journal of cell communication and signaling · 2025Article
- Deubiquitinase OTUD6A alleviates acetaminophen-induced liver injury by targeting EZH2 to reduce cell death in hepatocytes.Acta pharmaceutica Sinica. B · 2025Article
- NADTrends in molecular medicine · 2025Review
- Epigenetic therapeutics attenuate kidney injury and fibrosis by restoring the expression of epigenetically reprogrammed fibrogenic genes and signaling pathways.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2025Article
- Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury After Massive Burns.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- Nucleic acid and protein methylation modification in renal diseases.Acta pharmacologica Sinica · 2024Review
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Discovery of ferroptosis-related genes in renal ischemia reperfusion and evaluate the potential impact on kidney transplantation.Frontiers in immunology · 2024Article
- microRNA-29b-3p attenuates diabetic nephropathy in mice by modifying EZH2.Hormones (Athens, Greece) · 2023Article
- 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
- Histone Modifications in Acute Kidney Injury.Kidney diseases (Basel, Switzerland) · 2022Review
- 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
- Selective EZH2 inhibitor zld1039 alleviates inflammation in cisplatin-induced acute kidney injury partially by enhancing RKIP and suppressing NF-κB p65 pathway.Acta pharmacologica Sinica · 2022Article
- LncRNA ANRIL mediates endothelial dysfunction through BDNF downregulation in chronic kidney disease.Cell death & disease · 2022Article
- Demethylation of H3K9 and H3K27 Contributes to the Tubular Renal Damage Triggered by Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Despite the established oncogenic and profibrotic functions of enhancer of zeste homolog 2 (EZH2), a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3), its role in acute kidney injury (AKI) remains unclear. In this study, we demonstrated that EZH2 and H3K27me3 were upregulated in the murine kidney with AKI induced by either ischemia-reperfusion (I/R) or folic acid (FA). Pharmacologic inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) prevented tubular injury in both models as demonstrated by reduced renal dysfunction, diminished neutrophil gelatinase-associated lipocalin expression and decreased renal tubular cell death. Injury to the kidney resulted in reduced expression of E-cadherin and ZO-1, whereas EZH2 inhibition largely preserved their expression. Moreover, 3-DZNep was effective in counteracting the increased expression of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the phosphorylation of Raf-1 and ERK1/2 in the injured kidney. Conversely, blocking EZH2 reversed the decrease of tissue inhibitor of metalloproteinase (TIMP)-2 and metalloproteinase (TIMP)-3, and Raf kinase inhibitor protein (RKIP) in the kidney after acute injury. Similarly, oxidant injury to cultured kidney proximal tubular epithelial cells caused a decrease in the expression of E-cadherin, ZO-1, TIMP-2/-3, and RKIP, as well as an increase in the expression of MMP-2/9 and phosphorylation of Raf-1 ERK1/2. Blocking EZH2 with 3-DZNep or SiRNA hindered these responses. Thus, these results suggest that targeting EZH2 protects against AKI through a mechanism associated with the preservation of adhesion/junctions, reduction of matrix metalloproteinases and attenuation of the Raf-1/ERK1/2 pathway.
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