ArticleScientific reports2019
An immortalized cell line derived from renal erythropoietin-producing (REP) cells demonstrates their potential to transform into myofibroblasts.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- The Lung-Kidney Axis: A Coordinated Regulation of Oxygen Sensing and Erythropoiesis.Biomedicines · 2026Review
- Anemia in diabetes mellitus: Pathogenetic aspects and the value of early erythropoietin therapy.Metabolism open · 2025Review
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Article
- Review
- Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.International urology and nephrology · 2024Review
- Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.Journal of clinical biochemistry and nutrition · 2024Article
- Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury.International journal of molecular sciences · 2024Article
- Article
- Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.Nature reviews. Nephrology · 2023Review
- Progress in the Detection of Erythropoietin in Blood, Urine, and Tissue.Molecules (Basel, Switzerland) · 2023Review
- Relationship between haemodynamic indicators and haemogram in patients with heart failure.ESC heart failure · 2023Article
- Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism.International journal of molecular sciences · 2023Review
- 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
- 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
- Article
- Effects of Roxadustat on Erythropoietin Production in the Rat Body.Molecules (Basel, Switzerland) · 2022Article
- Efficient isolation of interstitial fibroblasts directly from mouse kidneys or indirectly afterSTAR protocols · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The erythroid growth factor erythropoietin (Epo) is produced by renal interstitial fibroblasts, called REP (renal Epo-producing) cells, in a hypoxia-inducible manner. In chronic kidney disease (CKD), REP cells lose their Epo-production ability, leading to renal anaemia. Concurrently, REP cells are suggested to be transformed into myofibroblasts, which are the major player of renal fibrosis. Although establishment of cultured cell lines derived from REP cells has been a long-term challenge, we here successfully established a REP-cell-derived immortalized and cultivable cell line (Replic cells) by using a genetically modified mouse line. Replic cells exhibited myofibroblastic phenotypes and lost their Epo-production ability, reflecting the situation in renal fibrosis. Additionally, we found that cell-autonomous TGFβ signalling contributes to maintenance of the myofibroblastic features of Replic cells. Furthermore, the promoters of genes for Epo and HIF2α, a major activator of Epo gene expression, were highly methylated in Replic cells. Thus, these results strongly support our contention that REP cells are the origin of myofibroblasts in fibrotic kidneys and demonstrate that cell-autonomous TGFβ signalling and epigenetic silencing are involved in renal fibrosis and renal anaemia, respectively, in CKD. The Replic cell line is a useful tool to further investigate the molecular mechanisms underlying renal fibrosis.
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