ArticleKidney international2013
The erythropoietin receptor is a downstream effector of Klotho-induced cytoprotection.
Article in Kidney international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Effect of essential amino acid кetoanalogues and protein restriction diet on morphogenetic proteins (FGF-23 and Кlotho) in 3b-4 stages chronic кidney disease patients: a randomized pilot study.Clinical and experimental nephrology · 2018Trial
- Erythropoietin receptor upregulation is associated with tubular injury severity in human acute kidney injury.Renal failure · 2026Article
- Therapeutic Effects of Nanoparticles Loaded with Combined Sense and Anti-Sense of EpoR Plasmids to Enhance Angiogenesis.Research square · 2026Article
- Extracellular Vesicles as Mediators of Endothelial and Tubular Injury in Cardiac Surgery-Associated Acute Kidney Injury.Biomedicines · 2026Review
- Klotho microinjection into the RVLM attenuates acute kidney injuryResearch in pharmaceutical sciences · 2025Article
- Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing renal senescence induced by calcium oxalate crystals.Urolithiasis · 2025Article
- Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.Molecular biomedicine · 2025Review
- Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm.International journal of molecular sciences · 2025Review
- HBSP inhibits tubular cell pyroptosis and apoptosis, promotes macrophage M2 polarization, and protects LPS-induced acute kidney injury.Journal of cellular and molecular medicine · 2024Article
- Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Administration of α-Klotho Does Not Rescue Renal Anemia in Mice.Frontiers in pediatrics · 2022Article
- Molecular mechanisms and physiological functions of autophagy in kidney diseases.Frontiers in pharmacology · 2022Review
- Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease.Pharmaceutics · 2021Review
- The Source Matters-Effects of High Phosphate Intake from Eight Different Sources in Dogs.Animals : an open access journal from MDPI · 2021Article
- The protective mechanism of Klotho gene-modified bone marrow mesenchymal stem cells on acute kidney injury induced by rhabdomyolysis.Regenerative therapy · 2021Review
- The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease.Toxins · 2021Article
- Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor.Kidney international reports · 2021Article
- Erythropoietin Receptor/β Common Receptor: A Shining Light on Acute Kidney Injury Induced by Ischemia-Reperfusion.Frontiers in immunology · 2021Review
- Intranasal injection of recombinant human erythropoietin improves cognitive and visual impairments in chronic cerebral ischemia rats.Biomedical reports · 2020Article
- Advances in Understanding the Effects of Erythropoietin on Renal Fibrosis.Frontiers in medicine · 2020Review
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9 authors at 2 institutions in 2 countries.
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Abstract
Although the role of the erythropoietin (EPO) receptor (EpoR) in erythropoiesis has been known for decades, its role in nonhematopoietic tissues is still not well defined. Klotho has been shown and EPo has been suggested to protect against acute ischemia-reperfusion injury in the kidney. Here we found in rat kidney and in a rat renal tubular epithelial cell line (NRK cells) EpoR transcript and antigen, and EpoR activity signified as EPo-induced phosphorylation of Jak2, ErK, Akt, and Stat5 indicating the presence of functional EpoR. Transgenic overexpression of Klotho or addition of exogenous recombinant Klotho increased kidney EpoR protein and transcript. In NRK cells, Klotho increased EpoR protein, enhanced EPo-triggered phosphorylation of Jak2 and Stat5, the nuclear translocation of phospho-Stat5, and protected NRK cells from hydrogen peroxide cytotoxicity. Knockdown of endogenous EpoR rendered NRK cells more vulnerable, and overexpression of EpoR more resistant to peroxide-induced cytotoxicity, indicating that EpoR mitigates oxidative damage. Knockdown of EpoR by siRNA abolished Epo-induced Jak2, and Stat5 phosphorylation, and blunted the protective effect of Klotho against peroxide-induced cytotoxicity. Thus in the kidney, EpoR and its activity are downstream effectors of Klotho enabling it to function as a cytoprotective protein against oxidative injury.
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