ArticleThe Journal of clinical investigation2019
FoxO3 activation in hypoxic tubules prevents chronic kidney disease.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 105 citations in OpenAlex.
- Global Adam17 Deficiency Preserves Renal Function and Modulates Integrated Pathogenic Responses in Experimental Diabetic Kidney Disease.International journal of molecular sciences · 2026Article
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- The gut-kidney axis in high-altitude hypoxia: pathophysiological mechanisms and the central role of hypoxia inducible factor.Annals of medicine · 2025Review
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Dynamic regulation of proximal tubular autophagy from injury to repair after ischemic kidney damage.Cellular & molecular biology letters · 2024Article
- αKlotho modulates BNIP3-mediated mitophagy by regulating FoxO3 to decrease mitochondrial ROS and apoptosis in contrast-induced acute kidney injury.Cellular and molecular life sciences : CMLS · 2024Article
- Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.Nature genetics · 2024Article
- Review
- MondoA and AKI and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2024Article
- EValuating the Effect of periopeRaTIve empaGliflOzin on cardiac surgery associated acute kidney injury: rationale and design of the VERTIGO study.Clinical kidney journal · 2024Article
- The Role of Mitochondrial Sirtuins (SIRT3, SIRT4 and SIRT5) in Renal Cell Metabolism: Implication for Kidney Diseases.International journal of molecular sciences · 2024Review
- Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.bioRxiv : the preprint server for biology · 2024Article
- Recent Update on Acute Kidney Injury-to-Chronic Kidney Disease Transition.Yonsei medical journal · 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
- From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity.Acta pharmacologica Sinica · 2023Article
- SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.International journal of molecular sciences · 2023Article
- FoxO3 and oxidative stress: a multifaceted role in cellular adaptation.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Ketogenic Diet and Ketone Bodies against Ischemic Injury: Targets, Mechanisms, and Therapeutic Potential.International journal of molecular sciences · 2023Review
7 more citing papers are in PubMed but not listed here.
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6 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute kidney injury (AKI) can lead to chronic kidney disease (CKD) if injury is severe and/or repair is incomplete. However, the pathogenesis of CKD following renal ischemic injury is not fully understood. Capillary rarefaction and tubular hypoxia are common findings during the AKI to CKD transition. We investigated the tubular stress response to hypoxia and demonstrated that a stress responsive transcription factor, FoxO3, was regulated by prolyl hydroxylase. Hypoxia inhibited FoxO3 prolyl hydroxylation and FoxO3 degradation, thus leading to FoxO3 accumulation and activation in tubular cells. Hypoxia-activated Hif-1α contributed to FoxO3 activation and functioned to protect kidneys, as tubular deletion of Hif-1α decreased hypoxia-induced FoxO3 activation, and resulted in more severe tubular injury and interstitial fibrosis following ischemic injury. Strikingly, tubular deletion of FoxO3 during the AKI to CKD transition aggravated renal structural and functional damage leading to a more profound CKD phenotype. We showed that tubular deletion of FoxO3 resulted in decreased autophagic response and increased oxidative injury, which may explain renal protection by FoxO3. Our study indicates that in the hypoxic kidney, stress responsive transcription factors can be activated for adaptions to counteract hypoxic insults, thus attenuating CKD development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.