ArticleScientific reports2017
Selective tubular activation of hypoxia-inducible factor-2α has dual effects on renal fibrosis.
Article in Scientific reports, 2017. 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, 40 citations in OpenAlex.
- Association of serums HIF-1α and HIF-2α with the levels and severity of renal fibrosis: a retrospective cohort study.BMC nephrology · 2026Article
- Article
- The gut-kidney axis in high-altitude hypoxia: pathophysiological mechanisms and the central role of hypoxia inducible factor.Annals of medicine · 2025Review
- Characteristics and Outcomes of IgA Nephropathy Patients With SGLT2 Inhibitor-Induced Polycythemia.Cureus · 2025Article
- Article
- The role of hypoxia-inducible factors 1 and 2 in the pathogenesis of diabetic kidney disease.Journal of nephrology · 2025Review
- Reduced glomerular and elevated tubulointerstitial transglutaminase pathway and its inhibition in a rat model of renal warm ischemia: implications for feline chronic kidney disease.Frontiers in veterinary science · 2025Article
- Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?Journal of veterinary pharmacology and therapeutics · 2025Review
- Long-term treatment of chronic kidney disease patients with anemia using hypoxia-inducible factor prolyl hydroxylase inhibitors: potential concerns.Pediatric nephrology (Berlin, Germany) · 2024Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Effects of long-term tubular HIF-2α overexpression on progressive renal fibrosis in a chronic kidney disease model.BMB reports · 2023Article
- No benefit of HIF prolyl hydroxylase inhibition for hypertensive renal damage in renovascular hypertensive rats.Frontiers in physiology · 2023Article
- Addition of glomerular lesion severity improves the value of anemia status for the prediction of renal outcomes in Chinese patients with type 2 diabetes.Renal failure · 2022Observational
- New Approaches to Diabetic Nephropathy from Bed to Bench.Biomedicines · 2022Review
- Review
- Sodium-Glucose Cotransporter 2 Inhibitors Work as a "Regulator" of Autophagic Activity in Overnutrition Diseases.Frontiers in pharmacology · 2021Review
- Role of hypoxia in inhibiting dendritic cells by VEGF signaling in tumor microenvironments: mechanism and application.American journal of cancer research · 2021Review
- Mutual Antagonism of Hypoxia-Inducible Factor Isoforms in Cardiac, Vascular, and Renal Disorders.JACC. Basic to translational science · 2020Review
- Endothelial prolyl hydroxylase 2 is necessary for angiotensin II-mediated renal fibrosis and injury.American journal of physiology. Renal physiology · 2020Article
- Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors.Journal of the American Society of Nephrology : JASN · 2020Review
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.
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