ArticleThe Journal of clinical investigation2016
DNA methyltransferase inhibition restores erythropoietin production in fibrotic murine kidneys.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- Cell-Specific Roles of Angiopoietin-2 in CKD.Journal of the American Society of Nephrology : JASN · 2026Article
- The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl-4-hydroxylases 2 and 3.The Journal of physiology · 2026Article
- CaMKKβ regulates transcription factor Elf2 gene methylation to maintain endothelial junctional barrier integrity.iScience · 2026Article
- The Inflammatory Milieu Exacerbates Anemia of Chronic Kidney Disease: From the Gut-Kidney Axis to Bone Marrow Hematopoiesis Inhibition.Kidney & blood pressure research · 2026Review
- Chromatin remodeling and epigenetic regulation in chronic kidney disease.Frontiers in genetics · 2026Review
- The Role of DNA Methyltransferases in Urinary System Diseases.Cancer innovation · 2025Review
- Hypoxia-inducible factor-2 stabilization is not sufficient to induce erythropoietin production in deeper medullary fibroblasts.The Journal of physiology · 2025Article
- Pericytes in tissue fibrosis.American journal of physiology. Cell physiology · 2025Review
- Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A.Diabetes & metabolism journal · 2025Article
- Article
- Epigenetics of Hypertensive Nephropathy.Biomedicines · 2024Review
- Targeting inflammation in perivascular cells and neuroimmune interactions for treating kidney disease.Clinical and experimental nephrology · 2024Review
- Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.Journal of clinical biochemistry and nutrition · 2024Article
- Hypoxic Inducible Factor Stabilization in Pericytes beyond Erythropoietin Production: The Good and the Bad.Antioxidants (Basel, Switzerland) · 2024Review
- Mechanosensitive Cation Channel Piezo1 Is Involved in Renal Fibrosis Induction.International journal of molecular sciences · 2024Review
- Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium-glucose cotransporter 2 inhibitors.European heart journal · 2023Article
- Review
- Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.Nature reviews. Nephrology · 2023Review
- Novel Approaches in Chronic Renal Failure without Renal Replacement Therapy: A Review.Biomedicines · 2023Review
- The transcriptional and regulatory identity of erythropoietin producing cells.Nature medicine · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal erythropoietin-producing cells (REPCs) remain in the kidneys of patients with chronic kidney disease, but these cells do not produce sufficient erythropoietin in response to hypoxic stimuli. Treatment with HIF stabilizers rescues erythropoietin production in these cells, but the mechanisms underlying the decreased response of REPCs in fibrotic kidneys to anemic stimulation remain elusive. Here, we show that fibroblast-like FOXD1+ progenitor-derived kidney pericytes, which are characterized by the expression of α1 type I collagen and PDGFRβ, produce erythropoietin through HIF2α regulation but that production is repressed when these cells differentiate into myofibroblasts. DNA methyltransferases and erythropoietin hypermethylation are upregulated in myofibroblasts. Exposure of myofibroblasts to nanomolar concentrations of the demethylating agent 5-azacytidine increased basal expression and hypoxic induction of erythropoietin. Mechanistically, the profibrotic factor TGF-β1 induced hypermethylation and repression of erythropoietin in pericytes; these effects were prevented by 5-azacytidine treatment. These findings shed light on the molecular mechanisms underlying erythropoietin repression in kidney myofibroblasts and demonstrate that clinically relevant, nontoxic doses of 5-azacytidine can restore erythropoietin production and ameliorate anemia in the setting of kidney fibrosis in mice.
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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.