ArticlePloS one2018
The hypoxia inducible factor/erythropoietin (EPO)/EPO receptor pathway is disturbed in a rat model of chronic kidney disease related anemia.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Therapeutic role of erythropoietin in methanol induced optic neuropathy: a systematic review.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2024Pooled it
- Beyond traditional roles: vitamin D and erythropoietin as immune modulators in kidney diseases.Clinical kidney journal · 2026Review
- The Lung-Kidney Axis: A Coordinated Regulation of Oxygen Sensing and Erythropoiesis.Biomedicines · 2026Review
- Underlying Mechanisms of Osteoporosis in the Context of Multimorbidity: Clinical Challenges and Management Strategies.Nutrients · 2026Review
- Current research on the HIF-2α-EPO-Hb axis in hypoxic environments: from molecular mechanisms to clinical.Frontiers in medicine · 2026Review
- Lineage-Specific Disruption of Hematopoiesis by Oxaliplatin: Mechanisms of Erythropoietin Resistance and Immune Suppression.Journal of hematology and oncology research · 2026Article
- High-altitude polycythemia: State-of-the-art review.Therapeutic advances in hematology · 2026Review
- Challenges in mimicking hypoxia: insights into HIF-regulated MiRNA expression induced by DMOG and CoClCell communication and signaling : CCS · 2025Article
- The role of hypoxia-inducible factors 1 and 2 in the pathogenesis of diabetic kidney disease.Journal of nephrology · 2025Review
- Anemia and Mineral Bone Disorder in Kidney Disease Patients: The Role of FGF-23 and Other Related Factors.International journal of molecular sciences · 2024Review
- Leukopenia in autosomal dominant polycystic kidney disease: a single-center cohort of kidney transplant candidates with post-transplantation follow-up.Clinical kidney journal · 2023Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.British journal of cancer · 2023Review
- Fibroblast Growth Factor 23 Bone Regulation and Downstream Hormonal Activity.Calcified tissue international · 2023Review
- Erythropoietin promotes energy metabolism to improve LPS-induced injury in HK-2 cells via SIRT1/PGC1-α pathway.Molecular and cellular biochemistry · 2023Article
- Arteriovenous Fistulae in Chronic Kidney Disease and the Heart: Physiological, Histological, and Transcriptomic Characterization of a Novel Rat Model.Journal of the American Heart Association · 2022Article
- Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.International journal of molecular sciences · 2022Review
- The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexes and HIF-2 induced miRNAs in human endothelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Tipping the balance between erythroid cell differentiation and induction of anemia in response to the inflammatory pathology associated with chronic trypanosome infections.Frontiers in immunology · 2022Article
- Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesAnemia is a known driver for hypoxia inducible factor (HIF) which leads to increased renal erythropoietin (EPO) synthesis. Bone marrow (BM) EPO receptor (EPOR) signals are transduced through a JAK2-STAT5 pathway. The origins of anemia of chronic kidney disease (CKD) are multifactorial, including impairment of both renal EPO synthesis as well as intestinal iron absorption. We investigated the HIF- EPO- EPOR axis in kidney, BM and proximal tibia in anemic juvenile CKD rats.
methodsCKD was induced by 5/6 nephrectomy in young (20 days old) male Sprague-Dawley rats while C group was sham operated. Rats were sacrificed 4 weeks after CKD induction and 5 minutes after a single bolus of IV recombinant human EPO. An additional control anemic (C-A) group was daily bled for 7 days.
resultsHemoglobin levels were similarly reduced in CKD and C-A (11.4 ± 0.3 and 10.8±0.2 Vs 13.5±0.3 g/dL in C, p<0.0001). Liver hepcidin mRNA was decreased in CA but increased in CKD. Serum iron was unchanged while transferrin levels were mildly decreased in CKD. Kidney HIF2α protein was elevated in C-A but unchanged in CKD. Kidney EPO protein and mRNA levels were unchanged between groups. However, BM EPO protein (which reflects circulating EPO) was increased in C-A but remained unchanged in CKD. BM and proximal tibia EPOR were unchanged in C-A but decreased in CKD. Proximal tibial phospho-STAT5 increased after the EPO bolus in C but not in CKD.
conclusionsCompared to blood loss, anemia in young CKD rats is associated with inappropriate responses in the HIF-EPO-EPO-R axis: kidney HIF2α and renal EPO are not increased, BM and bone EPOR levels, as well as bone pSTAT5 response to EPO are reduced. Thus, anemia of CKD may be treated with additional therapeutic avenues beyond iron and EPO supplementation.
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