ArticleThe Journal of clinical investigation2011
Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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Who cites it
189 citing papers in PubMed, 342 citations in OpenAlex.
- Article
- Biological maturation drives the hepatic-to-renal switch in erythropoietin production at birth.EBioMedicine · 2026Article
- Fibroblast-derived neuropilin 1 alleviates renal fibrosis progression.The Journal of pathology · 2026Article
- Glutathione Synthesis via the Cystine/Glutamate Transporter Promotes the Formation of Tertiary Lymphoid Structures in the Kidney.Journal of the American Society of Nephrology : JASN · 2026Article
- A kappa opioid receptor agonist, difelikefalin, improves acute kidney injury in experimental sepsis models.PloS one · 2026Article
- Tracing the origin of myofibroblasts in kidney fibrosis.Nature communications · 2025Article
- Article
- Mitochondrial dysfunction: the hidden catalyst in chronic kidney disease progression.Renal failure · 2025Review
- Polycythemia secondary to renal dromedary hump in a young healthy woman: a case report.Journal of medical case reports · 2025Article
- Prognostic Impact of Anemia in Patients with Significant Mitral Regurgitation: A Multicenter Cohort Study.International journal of general medicine · 2025Article
- Aligning cellular and molecular components in age-dependent tertiary lymphoid tissues of kidney and liver.PloS one · 2025Article
- Insoluble HIFa protein aggregates by cadmium disrupt hypoxia-prolyl hydroxylase (PHD)-hypoxia inducible factor (HIFa) signaling in renal epithelial (NRK-52E) and interstitial (FAIK3-5) cells.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- Piezo ion channels: long-sought-after mechanosensors mediating hypertension and hypertensive nephropathy.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Targeting inflammation in perivascular cells and neuroimmune interactions for treating kidney disease.Clinical and experimental nephrology · 2024Review
- Anemia of Chronic Kidney Disease-A Narrative Review of Its Pathophysiology, Diagnosis, and Management.Biomedicines · 2024Review
- Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.Journal of clinical biochemistry and nutrition · 2024Article
- Iron Metabolism and Inflammatory Mediators in Patients with Renal Dysfunction.International journal of molecular sciences · 2024Review
- Permissive role of vascular endothelium in fibrosis: focus on the kidney.American journal of physiology. Cell physiology · 2024Review
- Propolis and its therapeutic effects on renal diseases: A review.Iranian journal of basic medical sciences · 2024Review
- Exploring unconventional targets in myofibroblast transdifferentiation outside classical TGF-Frontiers in physiology · 2024Review
129 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced production of fibroblast-derived erythropoietin, a hormone that stimulates erythropoiesis. Despite their importance in chronic kidney disease, the origin and regulatory mechanism of fibroblasts remain unclear. Here, we have demonstrated that the majority of erythropoietin-producing fibroblasts in the healthy kidney originate from myelin protein zero-Cre (P0-Cre) lineage-labeled extrarenal cells, which enter the embryonic kidney at E13.5. In the diseased kidney, P0-Cre lineage-labeled fibroblasts, but not fibroblasts derived from injured tubular epithelial cells through epithelial-mesenchymal transition, transdifferentiated into myofibroblasts and predominantly contributed to fibrosis, with concomitant loss of erythropoietin production. We further demonstrated that attenuated erythropoietin production in transdifferentiated myofibroblasts was restored by the administration of neuroprotective agents, such as dexamethasone and neurotrophins. Moreover, the in vivo administration of tamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well as fibrosis in a mouse model of kidney fibrosis. These findings reveal the pathophysiological roles of P0-Cre lineage-labeled fibroblasts in the kidney and clarify the link between renal fibrosis and renal anemia.
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