ArticleJournal of the American Society of Nephrology : JASN2015
Chronic hypoxia-inducible transcription factor-2 activation stably transforms juxtaglomerular renin cells into fibroblast-like cells in vivo.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men.Pflugers Archiv : European journal of physiology · 2018Trial
- The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl-4-hydroxylases 2 and 3.The Journal of physiology · 2026Article
- The gut-kidney axis in high-altitude hypoxia: pathophysiological mechanisms and the central role of hypoxia inducible factor.Annals of medicine · 2025Review
- Hypoxia-inducible factor-2 stabilization is not sufficient to induce erythropoietin production in deeper medullary fibroblasts.The Journal of physiology · 2025Article
- Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Flexible and multifaceted: the plasticity of renin-expressing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Renin Cells, the Kidney, and Hypertension.Circulation research · 2021Review
- Deciphering the Identity of Renin Cells in Health and Disease.Trends in molecular medicine · 2021Review
- VEGF expands erythropoiesis via hypoxia-independent induction of erythropoietin in noncanonical perivascular stromal cells.The Journal of experimental medicine · 2019Article
- Renin cells in homeostasis, regeneration and immune defence mechanisms.Nature reviews. Nephrology · 2018Review
- Juxtaglomerular Cell Phenotypic Plasticity.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2017Review
- Endocrine functions of the renal interstitium.Pflugers Archiv : European journal of physiology · 2017Review
- Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology.Hypertension (Dallas, Tex. : 1979) · 2017Article
- Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin.The Journal of clinical investigation · 2016Article
- Hypoxia-Inducible Factor Stabilizers: a New Avenue for Reducing BP While Helping Hemoglobin?Current hypertension reports · 2016Review
- Cells of renin lineage express hypoxia inducible factor 2α following experimental ureteral obstruction.BMC nephrology · 2016Article
- Inducible glomerular erythropoietin production in the adult kidney.Kidney international · 2015Article
- Anaemia in kidney disease: harnessing hypoxia responses for therapy.Nature reviews. Nephrology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
On the basis of previous observations that deletion of the von Hippel-Lindau protein (pVHL) in juxtaglomerular (JG) cells of the kidney suppresses renin and induces erythropoietin expression, this study aimed to characterize the events underlying this striking change of hormone expression. We found that renin cell-specific deletion of pVHL in mice leads to a phenotype switch in JG cells, from a cuboid and multiple vesicle-containing form into a flat and elongated form without vesicles. This shift of cell phenotype was accompanied by the disappearance of marker proteins for renin cells (e.g., aldo-keto reductase family 1, member 7 and connexin 40) and by the appearance of markers of fibroblast-like cells (e.g., collagen I, ecto-5'-nucleotidase, and PDGF receptor-β). Furthermore, hypoxia-inducible transcription factor-2α (HIF-2α) protein constitutively accumulated in these transformed cells. Codeletion of pVHL and HIF-2α in JG cells completely prevented the phenotypic changes. Similar to renin expression in normal JG cells, angiotensin II negatively regulated erythropoietin expression in the transformed cells. In summary, chronic activation of HIF-2 in renal JG cells leads to a reprogramming of the cells into fibroblast-like cells resembling native erythropoietin-producing cells located in the tubulointerstitium.
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