ArticleThe Journal of clinical investigation2016
Renal epithelium regulates erythropoiesis via HIF-dependent suppression of erythropoietin.
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 35 papers.
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35 citing papers in PubMed.
- Article
- Two Cases of Giant Uterine Leiomyomas With Myomatous Erythrocytosis Syndrome Treated by Laparoscopic Hysterectomy.Cureus · 2025Article
- Regional metabolic analysis of structurally preserved kidney slices by ex vivo respirometry.American journal of physiology. Renal physiology · 2025Article
- Acute kidney injury through a metabolic lens: pathological reprogramming mechanisms and clinical translation potential.Frontiers in physiology · 2025Review
- Multiple roles of mitochondrial autophagy receptor FUNDC1 in mitochondrial events and kidney disease.Frontiers in cell and developmental biology · 2024Review
- Hypoxia-inducible factors and essential hypertension: narrative review of experimental and clinical data.Pharmacological reports : PR · 2023Review
- Gliflozins, Erythropoietin, and Erythrocytosis: Is It Renal Normoxia- or Hypoxia-Driven?Journal of clinical medicine · 2023Article
- Updated perspective of EPAS1 and the role in pulmonary hypertension.Frontiers in cell and developmental biology · 2023Review
- Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Neurogenic and pericytic plasticity of conditionally immortalized cells derived from renal erythropoietin-producing cells.Journal of cellular 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
- [Characteristics of bone marrow compensatory erythropoiesis in hereditary spherocytosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- Stabilization of hypoxia-inducible factor ameliorates glomerular injury sensitization after tubulointerstitial injury.Kidney international · 2021Article
- Evolving Medical Imaging Techniques for the Assessment of Delayed Graft Function: A Narrative Review.Canadian journal of kidney health and disease · 2021Review
- Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.International journal of molecular sciences · 2020Review
- Glucose transporters in the kidney in health and disease.Pflugers Archiv : European journal of physiology · 2020Review
- HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice.Nature communications · 2020Article
- Association between serum erythropoietin levels and renal reversibility in patients with renal impairment from multiple myeloma.Cancer medicine · 2020Article
- The tubular hypothesis of nephron filtration and diabetic kidney disease.Nature reviews. Nephrology · 2020Review
- Micro-Rheological Changes of Red Blood Cells in the Presence of an Arterio-Venous Fistula or a Loop-Shaped Venous Graft in the Rat.Frontiers in physiology · 2020Article
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Abstract
The adult kidney plays a central role in erythropoiesis and is the main source of erythropoietin (EPO), an oxygen-sensitive glycoprotein that is essential for red blood cell production. Decreases of renal pO2 promote hypoxia-inducible factor 2-mediated (HIF-2-mediated) induction of EPO in peritubular interstitial fibroblast-like cells, which serve as the cellular site of EPO synthesis in the kidney. It is not clear whether HIF signaling in other renal cell types also contributes to the regulation of EPO production. Here, we used a genetic approach in mice to investigate the role of renal epithelial HIF in erythropoiesis. Specifically, we found that HIF activation in the proximal nephron via induced inactivation of the von Hippel-Lindau tumor suppressor, which targets the HIF-α subunit for proteasomal degradation, led to rapid development of hypoproliferative anemia that was associated with a reduction in the number of EPO-producing renal interstitial cells. Moreover, suppression of renal EPO production was associated with increased glucose uptake, enhanced glycolysis, reduced mitochondrial mass, diminished O2 consumption, and elevated renal tissue pO2. Our genetic analysis suggests that tubulointerstitial cellular crosstalk modulates renal EPO production under conditions of epithelial HIF activation in the kidney.
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