ArticleJournal of the American Society of Nephrology : JASN2013
Plasticity of renal erythropoietin-producing cells governs fibrosis.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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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
104 citing papers in PubMed, 179 citations in OpenAlex.
- Safety and Efficacy of Vadadustat Versus Darbepoetin Alfa for Chronic Kidney Disease-Related Anemia in Patients Receiving Dialysis by Baseline Erythropoiesis-Stimulating Agent Dose.Hemodialysis international. International Symposium on Home Hemodialysis · 2026Trial
- (Pro)renin, Erythropoietin, Vitamin D and Urodilatin Release From Human Donor Kidneys During Normothermic Machine Perfusion: Predictors of Early Post-Transplant Outcome?Clinical transplantation · 2025Trial
- Macrophage-Fibroblast Crosstalk in Kidney Injury: A Narrative Review.International journal of molecular sciences · 2026Review
- Oxygenaging: A Physiological Framework for Geroscience.Aging cell · 2026Review
- Interstitial Fibrosis Severity Is Not Independently Associated with Anemia in Biopsy-Proven Primary Glomerulonephritis: A Nationwide Registry Analysis.Medicina (Kaunas, Lithuania) · 2026Article
- Cellular microenvironment of erythropoietin-producing cells in hypoxic and injured mouse kidneys.Experimental physiology · 2026Article
- A minimal mathematical model of red blood cell homeostasis in anemia.PLoS computational biology · 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
- Regenerative Versus Nonregenerative Repair of the Renal Medulla After Reversal of Ureteral Obstruction.Seminars in nephrology · 2025Review
- Uremic toxins levels are associated with miR-223 in chronic kidney disease-associated anemia.Non-coding RNA research · 2025Article
- A Mouse Model to Evaluate the Long-Term Structural and Functional Outcomes after the Reversal of Prolonged Unilateral Ureteric Obstruction.Journal of visualized experiments : JoVE · 2025Article
- Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A.Diabetes & metabolism journal · 2025Article
- Permanent defects in renal medullary structure and function after reversal of urinary obstruction.JCI insight · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
- Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.International urology and nephrology · 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
- Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction.International journal of molecular sciences · 2024Review
- Modification Effects of Albuminuria on the Association Between Kidney Function and Development of Anemia in Diabetes.The Journal of clinical endocrinology and metabolism · 2024Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CKD progresses with fibrosis and erythropoietin (Epo)-dependent anemia, leading to increased cardiovascular complications, but the mechanisms linking Epo-dependent anemia and fibrosis remain unclear. Here, we show that the cellular phenotype of renal Epo-producing cells (REPs) alternates between a physiologic Epo-producing state and a pathologic fibrogenic state in response to microenvironmental signals. In a novel mouse model, unilateral ureteral obstruction-induced inflammatory milieu activated NFκB and Smad signaling pathways in REPs, rapidly repressed the Epo-producing potential of REPs, and led to myofibroblast transformation of these cells. Moreover, we developed a unique Cre-based cell-fate tracing method that marked current and/or previous Epo-producing cells and revealed that the majority of myofibroblasts are derived from REPs. Genetic induction of NFκB activity selectively in REPs resulted in myofibroblastic transformation, indicating that NFκB signaling elicits a phenotypic switch. Reversing the unilateral ureteral obstruction-induced inflammatory microenvironment restored the Epo-producing potential and the physiologic phenotype of REPs. This phenotypic reversion was accelerated by anti-inflammatory therapy. These findings demonstrate that REPs possess cellular plasticity, and suggest that the phenotypic transition of REPs to myofibroblasts, modulated by inflammatory molecules, underlies the connection between anemia and renal fibrosis in CKD.
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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.