ArticlePloS one2011
Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Diet gel-based oral drug delivery system for controlled dosing of small molecules for microglia depletion and inducible Cre recombination in mice.Lab animal · 2025Article
- Cardiomyocyte crosstalk with endothelium modulates cardiac structure, function, and ischemia-reperfusion injury susceptibility through erythropoietin.Frontiers in physiology · 2024Article
- Erythropoietin and Skeletal Cells CrossTalks in Physiology and Disease.Current opinion in endocrine and metabolic research · 2023Article
- Effects of PHD and HSP90 on erythropoietin production in yak (Bos grunniens) renal interstitial fibroblast-like cells under hypoxia.Journal of molecular histology · 2022Article
- Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat.Clinical pharmacokinetics · 2022Review
- Induction of whole-body gene deletionFrontiers in pharmacology · 2022Article
- Differential Contribution of N- and C-Terminal Regions of HIF1α and HIF2α to Their Target Gene Selectivity.International journal of molecular sciences · 2020Article
- Endothelial cells by inactivation of VHL gene direct angiogenesis, not vasculogenesis via Twist1 accumulation associated with hemangioblastoma neovascularization.Scientific reports · 2017Article
- Role Of Hif2α Oxygen Sensing Pathway In Bronchial Epithelial Club Cell Proliferation.Scientific reports · 2016Article
- Erythropoietin and the use of a transgenic model of erythropoietin-deficient mice.Hypoxia (Auckland, N.Z.) · 2016Review
- HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction.Cardiovascular research · 2016Article
- Anaemia in kidney disease: harnessing hypoxia responses for therapy.Nature reviews. Nephrology · 2015Review
- Article
- Novel perspectives on the PHD-HIF oxygen sensing pathway in cardioprotection mediated by IPC and RIPC.Frontiers in physiology · 2015Review
- Regulation of erythropoiesis by hypoxia-inducible factors.Blood reviews · 2013Review
- Decreased VEGF expression and microvascular density, but increased HIF-1 and 2α accumulation and EPO expression in chronic moderate hyperoxia in the mouse brain.Brain research · 2012Article
- Microtubular stability affects pVHL-mediated regulation of HIF-1alpha via the p38/MAPK pathway in hypoxic cardiomyocytes.PloS one · 2012Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Von Hippel Lindau (Vhl) gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs), have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2). Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed)-UBC-Cre-ER(T2) adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo) gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2) tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2) mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.
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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.