ArticlePloS one2016
DNMT1 and HDAC2 Cooperate to Facilitate Aberrant Promoter Methylation in Inorganic Phosphate-Induced Endothelial-Mesenchymal Transition.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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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.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Endothelial-to-Mesenchymal Transition in Health and Disease: Molecular Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Calciprotein particle-activated endothelial cells aggravate smooth muscle cell calcification via paracrine signalling.Cellular and molecular life sciences : CMLS · 2025Article
- Molecular mechanisms of endothelial-mesenchymal transition and its pathophysiological feature in cerebrovascular disease.Cell & bioscience · 2025Review
- Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- HDAC2 as a target for developing anti-cancer drugs.Computational and structural biotechnology journal · 2023Review
- Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- EOS789, pan-phosphate transporter inhibitor, ameliorates the progression of kidney injury in anti-GBM-induced glomerulonephritis rats.Pharmacology research & perspectives · 2022Article
- Short communication: TNF-α and IGF-1 regulates epigenetic mechanisms of HDAC2 and HDAC10.PloS one · 2022Article
- Vascular Calcification Mechanisms: Updates and Renewed Insight into Signaling Pathways Involved in High Phosphate-Mediated Vascular Smooth Muscle Cell Calcification.Biomedicines · 2021Review
- Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease.Cell proliferation · 2021Review
- Inorganic Phosphate (Pi) Signaling in Endothelial Cells: A Molecular Basis for Generation of Endothelial Microvesicles in Uraemic Cardiovascular Disease.International journal of molecular sciences · 2020Article
- IRF1-mediated downregulation of PGC1α contributes to cardiorenal syndrome type 4.Nature communications · 2020Article
- DAXX mediates high phosphate-induced endothelial cell apoptosis in vitro through activating ERK signaling.PeerJ · 2020Article
- DNA methylation regulated gene expression in organ fibrosis.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- The role of epigenetics in renal ageing.Nature reviews. Nephrology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While phosphorus in the form of inorganic or organic phosphate is critically involved in most cellular functions, high plasma levels of inorganic phosphate levels have emerged as independent risk factor for cardiac fibrosis, cardiovascular morbidity and decreased life-expectancy. While the link of high phosphate and cardiovascular disease is commonly explained by direct cellular effects of phospho-regulatory hormones, we here explored the possibility of inorganic phosphate directly eliciting biological responses in cells. We demonstrate that human coronary endothelial cells (HCAEC) undergo an endothelial-mesenchymal transition (EndMT) when exposed to high phosphate. We further demonstrate that such EndMT is initiated by recruitment of aberrantly phosphorylated DNMT1 to the RASAL1 CpG island promoter by HDAC2, causing aberrant promoter methylation and transcriptional suppression, ultimately leading to increased Ras-GTP activity and activation of common EndMT regulators Twist and Snail. Our studies provide a novel aspect for known adverse effects of high phosphate levels, as eukaryotic cells are commonly believed to have lost phosphate-sensing mechanisms of prokaryotes during evolution, rendering them insensitive to extracellular inorganic orthophosphate. In addition, our studies provide novel insights into the mechanisms underlying specific targeting of select genes in context of fibrogenesis.
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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.