ArticleAmerican journal of physiology. Renal physiology2018
Effects of erythropoietin receptor activity on angiogenesis, tubular injury, and fibrosis in acute kidney injury: a "U-shaped" relationship.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Erythropoietin in Acute Kidney Injury (EAKI): a pragmatic randomized clinical trial.BMC nephrology · 2022Trial
- Impact of hemoglobin increase in patients with acute kidney injury and severe anemia on major adverse kidney events.Renal failure · 2026Article
- Erythropoietin receptor upregulation is associated with tubular injury severity in human acute kidney injury.Renal failure · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Advances in nephroprotection: the therapeutic role of selenium, silver, and gold nanoparticles in renal health.International urology and nephrology · 2025Review
- Co-treatment with erythropoietin derived HBSP and caspase-3 siRNA: A promising approach to prevent fibrosis after acute kidney injury.Journal of cellular and molecular medicine · 2024Article
- 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
- Erythropoietin Reduces Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Bleomycin-Induced Idiopathic Pulmonary Fibrosis.Journal of personalized medicine · 2024Article
- Tubular Endogenous Erythropoietin Protects Renal Function against Ischemic Reperfusion Injury.International journal of molecular sciences · 2024Article
- Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.Nature reviews. Nephrology · 2023Review
- HBSP improves kidney ischemia-reperfusion injury and promotes repair in properdin deficient miceFrontiers in immunology · 2023Article
- VEGFR2 insufficiency enhances phosphotoxicity and undermines Klotho's protection against peritubular capillary rarefaction and kidney fibrosis.American journal of physiology. Renal physiology · 2023Article
- In vivo evidence for therapeutic applications of beclin 1 to promote recovery and inhibit fibrosis after acute kidney injury.Kidney international · 2022Article
- Autophagy in renal fibrosis: Protection or promotion?Frontiers in pharmacology · 2022Review
- Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition.Frontiers in molecular biosciences · 2022Review
- Erythropoietin Mitigates Diabetic Nephropathy by Restoring PINK1/Parkin-Mediated Mitophagy.Frontiers in pharmacology · 2022Article
- Article
- The combination of vitamin D3 and erythropoietin alleviates acute kidney injury induced by ischemia-reperfusion via inhibiting inflammation and apoptosis.Iranian journal of basic medical sciences · 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
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knockin of wild-type human EpoR, which is hypofunctional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, more apoptosis at the acute stage (<7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days). In contrast, mice with hyperactive EpoR signaling from knockin of a constitutively active human EpoR had higher autophagic flux, milder kidney damage, and better renal function at the acute stage but, surprisingly, worse tubulointerstitial fibrosis and renal function at the subacute stage. Either excess or deficient EpoR activity in the kidney was associated with abnormal peritubular capillaries and tubular hypoxia, creating a "U-shaped" relationship. The direct effects of EpoR on tubular cells were confirmed in vitro by a hydrogen peroxide model using primary cultured proximal tubule cells with different EpoR activities. In summary, normal erythropoietin (EPO)/EpoR signaling in renal tubules provides defense against renal tubular injury maintains the autophagy-apoptosis balance and peritubular capillary integrity. High and low EPO/EpoR bioactivities both lead to vascular defect, and high EpoR activity overides the tubular protective effects in AKI recovery.
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