ArticlePloS one2011
Isolation and characterization of renal erythropoietin-producing cells from genetically produced anemia mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis.The Pan African medical journal · 2024Pooled it
- Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point.The journals of gerontology. Series A, Biological sciences and medical sciences · 2014Trial
- Roxadustat as a Hypoxia-Mimetic Agent: Erythropoietic Mechanisms, Bioanalytical Detection, and Regulatory Considerations in Sports Medicine.Current issues in molecular biology · 2025Review
- Phytoconstituents of Citrus limon (Lemon) as Potential Inhibitors Against Multi Targets of SARS-CoV-2 by Use of Molecular Modelling and In Vitro Determination Approaches.ChemistryOpen · 2024Article
- Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors as a New Treatment Option for Anemia in Chronic Kidney Disease.Biomedicines · 2024Review
- Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.Journal of clinical biochemistry and nutrition · 2024Article
- The role and clinical implications of HIF-PHI daprodustat in dialysis-dependent and non-dialysis-dependent chronic kidney disease anemic patients: a general review.Frontiers in nephrology · 2024Review
- Erythropoietin improves pulmonary hypertension by promoting the homing and differentiation of bone marrow mesenchymal stem cells in lung tissue.Human cell · 2024Article
- Erythropoietin levels after bilateral nephrectomy for renal cell carcinoma; a case report.Clinical and experimental nephrology · 2024Article
- Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice.Blood advances · 2023Article
- The transcriptional and regulatory identity of erythropoietin producing cells.Nature medicine · 2023Article
- Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism.International journal of molecular sciences · 2023Review
- Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Blockage of the Na-K-ATPase signaling-mediated oxidant amplification loop elongates red blood cell half-life and ameliorates uremic anemia induced by 5/6th PNx in C57BL/6 mice.American journal of physiology. Renal physiology · 2022Article
- Fate-mapping of erythropoietin-producing cells in mouse models of hypoxaemia and renal tissue remodelling reveals repeated recruitment and persistent functionality.Acta physiologica (Oxford, England) · 2022Article
- Efficient isolation of interstitial fibroblasts directly from mouse kidneys or indirectly afterSTAR protocols · 2021Article
- Transforming growth factor-β1 decreases erythropoietin production through repressing hypoxia-inducible factor 2α in erythropoietin-producing cells.Journal of biomedical science · 2021Article
- Article
- HIF-α Prolyl Hydroxylase Inhibitors and Their Implications for Biomedicine: A Comprehensive Review.Biomedicines · 2021Review
- Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the nature of renal erythropoietin-producing cells (REPs) remains a central challenge for elucidating the mechanisms involved in hypoxia and/or anemia-induced erythropoietin (Epo) production in adult mammals. Previous studies have shown that REPs are renal peritubular cells, but further details are lacking. Here, we describe an approach to isolate and characterize REPs. We bred mice bearing an Epo gene allele to which green fluorescent protein (GFP) reporter cDNA was knocked-in (Epo(GFP)) with mice bearing an Epo gene allele lacking the 3' enhancer (Epo(Δ3'E)). Mice harboring the mutant Epo(GFP/Δ3'E) gene exhibited anemia (average Hematocrit 18% at 4 to 6 days after birth), and this perinatal anemia enabled us to identify and purify REPs based on GFP expression from the kidney. Light and confocal microscopy revealed that GFP immunostaining was confined to fibroblastic cells that reside in the peritubular interstitial space, confirming our previous observation in Epo-GFP transgenic reporter assays. Flow cytometry analyses revealed that the GFP fraction constitutes approximately 0.2% of the whole kidney cells and 63% of GFP-positive cells co-express CD73 (a marker for cortical fibroblasts and Epo-expressing cells in the kidney). Quantitative RT-PCR analyses confirmed that Epo expression was increased by approximately 100-fold in the purified population of REPs compared with that of the unsorted cells or CD73-positive fraction. Gene expression analyses showed enrichment of Hif2α and Hif3α mRNA in the purified population of REPs. The genetic approach described here provides a means to isolate a pure population of REPs, allowing the analysis of gene expression of a defined population of cells essential for Epo production in the kidney. This has provided evidence that positive regulation by HIF2α and negative regulation by HIF3α might be necessary for correct renal Epo induction.
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Registered trials
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