ArticleJournal of the American Society of Nephrology : JASN2015
Activation of hypoxia-inducible factors prevents diabetic nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.Animal models and experimental medicine · 2023Pooled it
- How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Trial
- Renal Metabolic Rate of Oxygen in Response to Hypoxia Challenges by Means of Quantitative MRI in Humans.NMR in biomedicine · 2025Article
- Chronic Intermittent Low-Pressure Hypoxia Suppresses Inflammation and Regulates Glycolipids by Modulating Mitochondrial Respiration in db/db Mice.Metabolites · 2025Article
- MRI-based quantification of whole-organ renal metabolic rate of oxygen during free-breathing.Magnetic resonance in medicine · 2025Article
- Metformin alleviates renal tubular injury in diabetic kidney disease by activating mitophagy and inhibiting ferroptosis via HIF-1α/MIOX axis.Journal of pharmaceutical analysis · 2025Article
- Crosstalk between glomeruli and tubules.Nature reviews. Nephrology · 2025Review
- The role of hypoxia-inducible factors 1 and 2 in the pathogenesis of diabetic kidney disease.Journal of nephrology · 2025Review
- Risk factors for rapid kidney function decline in diabetes patients.Renal failure · 2024Review
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Article
- Adverse effects of acute tubular injury on the glomerulus: contributing factors and mechanisms.Pediatric nephrology (Berlin, Germany) · 2024Review
- Advances of Iron and Ferroptosis in Diabetic Kidney Disease.Kidney international reports · 2024Review
- VDR restores the expression of PINK1 and BNIP3 in TECs of streptozotocin-induced diabetic mice.Life science alliance · 2024Article
- Network analysis to explore the anti-senescence mechanism of Jinchan Yishen Tongluo Formula (JCYSTLF) in diabetic kidneys.Heliyon · 2024Article
- Quantification of whole-organ individual and bilateral renal metabolic rate of oxygen.Magnetic resonance in medicine · 2024Article
- The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.International journal of molecular sciences · 2024Review
- HIF-1 contributes to autophagy activation via BNIP3 to facilitate renal fibrosis in hypoxia in vitro and UUO in vivo.American journal of physiology. Cell physiology · 2024Article
- Evaluation of a deuterated triarylmethyl spin probe for in vivo RMagnetic resonance in medicine · 2024Article
- MRI-based quantification of whole-organ renal metabolic rate of oxygen.NMR in biomedicine · 2024Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs. We elucidated the involvement of oxidative stress by studying the effects of acute administration of the superoxide dismutase mimetic tempol. Compared with controls, diabetic rats displayed tissue hypoxia throughout the kidney, glomerular hyperfiltration, increased oxygen consumption, increased total mitochondrial leak respiration, and decreased tubular sodium transport efficiency. Diabetic kidneys showed proteinuria and tubulointerstitial damage. Cobalt chloride activated HIFs, prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, and kidney function, and reduced proteinuria and tubulointerstitial damage. The beneficial effects of tempol were less pronounced after activation of HIFs, indicating improved oxidative stress status. In conclusion, activation of HIFs prevents diabetes-induced alteration in kidney oxygen metabolism by normalizing glomerular filtration, which reduces tubular electrolyte load, preventing mitochondrial leak respiration and improving tubular transport efficiency. These improvements could be related to reduced oxidative stress and account for the reduced proteinuria and tubulointerstitial damage. Thus, pharmacologic activation of the HIF system may prevent development of diabetic nephropathy.
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