ArticleActa physiologica (Oxford, England)2022
Fate-mapping of erythropoietin-producing cells in mouse models of hypoxaemia and renal tissue remodelling reveals repeated recruitment and persistent functionality.
Article in Acta physiologica (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 26 citations in OpenAlex.
- The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl-4-hydroxylases 2 and 3.The Journal of physiology · 2026Article
- Cellular microenvironment of erythropoietin-producing cells in hypoxic and injured mouse kidneys.Experimental physiology · 2026Article
- Hypoxia-inducible factor-2 stabilization is not sufficient to induce erythropoietin production in deeper medullary fibroblasts.The Journal of physiology · 2025Article
- Inherent single-cell heterogeneity of the transcriptional response to hypoxia in cancer cells.NAR cancer · 2025Article
- Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.Clinical and translational medicine · 2025Review
- Phase-targeted erythropoietin derivatives for traumatic brain injury: bridging mechanisms to precision therapy.Frontiers in neurology · 2025Review
- The anaemia treatment journey of CKD patients: from epoetins to hypoxia-inducible factor-prolyl hydroxylase inhibitors.Clinical kidney journal · 2023Review
- The transcriptional and regulatory identity of erythropoietin producing cells.Nature medicine · 2023Article
- Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022Review
- EPO synthesis induced by HIF-PHD inhibition is dependent on myofibroblast transdifferentiation and colocalizes with non-injured nephron segments in murine kidney fibrosis.Acta physiologica (Oxford, England) · 2022Article
- 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
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimFibroblast-like renal erythropoietin (Epo) producing (REP) cells of the corticomedullary border region "sense" a decrease in blood oxygen content following anaemia or hypoxaemia. Burst-like transcription of Epo during tissue hypoxia is transient and is lost during fibrotic tissue remodelling, as observed in chronic kidney disease. The reason for this loss of Epo expression is under debate. Therefore, we tested the hypothesis that REP cell migration, loss and/or differentiation may cause Epo inhibition.
methodsUsing a reporter mouse that allows permanent labelling of active REP cells at any given time point, we analysed the spatiotemporal fate of REP cells following their initial hypoxic recruitment in models of hypoxaemia and renal tissue remodelling.
resultsIn long-term tracing experiments, tagged REP reporter cells neither died, proliferated, migrated nor transdifferentiated into myofibroblasts. Approximately 60% of tagged cells re-expressed Epo upon a second hypoxic stimulus. In an unilateral model of tissue remodelling, tagged cells proliferated and ceased to produce Epo before a detectable increase in myofibroblast markers. Treatment with a hypoxia-inducible factor (HIF) stabilizing agent (FG-4592/roxadustat) re-induced Epo expression in the previously active REP cells of the damaged kidney to a similar extent as in the contralateral healthy kidney.
conclusionsRather than cell death or differentiation, these results suggest cell-intrinsic transient inhibition of Epo transcription: following long-term dormancy, REP cells can repeatedly be recruited by tissue hypoxia, and during myofibrotic tissue remodelling, dormant REP cells are efficiently rescued by a pharmaceutic HIF stabilizer, demonstrating persistent REP cell functionality even during phases of Epo suppression.
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