ArticlePloS one2012
Renal tubular HIF-2α expression requires VHL inactivation and causes fibrosis and cysts.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- HIF sustain a transcriptional regulatory circuit of EPAS1 expression in renal clear cell carcinoma.Nature communications · 2026Article
- Discovery of tumor antigens in renal cell carcinoma and prospects for clinical application.Frontiers in immunology · 2026Review
- HIFα isoform specific activities drive cell-type specificity of VHL-associated oncogenesis.Nature communications · 2025Article
- Identification of autoantibodies against HIF1a in patients with anorexia nervosa and their potential role in hepatic cytolysis.Scientific reports · 2025Article
- Vitamin C Selectively Inhibits Kidney Renal Clear Cell Carcinoma Cell Growth by Suppressing the HIF-1 Pathway.OncoTargets and therapy · 2025Article
- Toward a CRISPR-based mouse model ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Idiopathic interstitial pneumonia in a patient with von Hippel-Lindau syndrome: a first case.ERJ open research · 2023Article
- von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology.Hematology/oncology clinics of North America · 2023Review
- Clinical findings, underlying pathogenetic processes and treatment of vascular dysfunction in autosomal dominant polycystic kidney disease.Renal failure · 2023Review
- No benefit of HIF prolyl hydroxylase inhibition for hypertensive renal damage in renovascular hypertensive rats.Frontiers in physiology · 2023Article
- Kidney in VHL disease: Early clear cell proliferation occurs in the distal tubular system.Oncology reports · 2022Article
- Flexible and multifaceted: the plasticity of renin-expressing cells.Pflugers Archiv : European journal of physiology · 2022Review
- Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism.Kidney diseases (Basel, Switzerland) · 2022Review
- Squalene deters drivers of RCC disease progression beyond VHL status.Cell biology and toxicology · 2021Article
- Hypoxic TAM-derived exosomal miR-155-5p promotes RCC progression through HuR-dependent IGF1R/AKT/PI3K pathway.Cell death discovery · 2021Article
- Clear cell renal cell carcinoma ontogeny and mechanisms of lethality.Nature reviews. Nephrology · 2021Review
- Contribution of Oxidative Stress to HIF-1-Mediated Profibrotic Changes during the Kidney Damage.Oxidative medicine and cellular longevity · 2021Review
- Targeting the HIF2-VEGF axis in renal cell carcinoma.Nature medicine · 2020Review
- Macrophage HIF-1α Is an Independent Prognostic Indicator in Kidney Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated α-subunits HIF-1α or HIF-2α. Both are regulated by oxygen dependent degradation, which is controlled by the tumor suppressor "von Hippel-Lindau" (VHL), the gatekeeper of renal tubular growth control. HIF appears to play a particular role for the kidney, where renal EPO production, organ preservation from ischemia-reperfusion injury and renal tumorigenesis are prominent examples. Whereas HIF-1α is inducible in physiological renal mouse, rat and human tubular epithelia, HIF-2α is never detected in these cells, in any species. In contrast, distinct early lesions of biallelic VHL inactivation in kidneys of the hereditary VHL syndrome show strong HIF-2α expression. Furthermore, knockout of VHL in the mouse tubular apparatus enables HIF-2α expression. Continuous transgenic expression of HIF-2α by the Ksp-Cadherin promotor leads to renal fibrosis and insufficiency, next to multiple renal cysts. In conclusion, VHL appears to specifically repress HIF-2α in renal epithelia. Unphysiological expression of HIF-2α in tubular epithelia has deleterious effects. Our data are compatible with dedifferentiation of renal epithelial cells by sustained HIF-2α expression. However, HIF-2α overexpression alone is insufficient to induce tumors. Thus, our data bear implications for renal tumorigenesis, epithelial differentiation and renal repair mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.