ArticleMolecular and cellular biology2009
A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 164 citations in OpenAlex.
- The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen.Breast cancer research : BCR · 2011Trial
- Endothelial prolyl hydroxylase 3 mitigates maladaptive inflammation to promote post-ischemic kidney repair.Kidney international · 2026Article
- Distinct HIF1α and HIF2α functions control skeletal muscle metabolism and erythropoiesis.The Journal of clinical investigation · 2026Article
- Cardioprotective effects of prolyl hydroxylase inhibitors during reperfusion in myocardial infarction: A study using cardiosphere-derived cells.Experimental physiology · 2026Article
- Hypoxia-inducible factor-2 stabilization is not sufficient to induce erythropoietin production in deeper medullary fibroblasts.The Journal of physiology · 2025Article
- Inherent single-cell heterogeneity of the transcriptional response to hypoxia in cancer cells.NAR cancer · 2025Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- The impact of aerobic and anaerobic exercise interventions on the management and outcomes of non-alcoholic fatty liver disease.Physiological research · 2024Review
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
- Cathepsins L and B target HIF1α for oxygen-independent proteolytic cleavage.Scientific reports · 2024Article
- Prolyl hydroxylase domain inhibitor is an effective pre-hospital pharmaceutical intervention for trauma and hemorrhagic shock.Scientific reports · 2024Article
- von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology.Hematology/oncology clinics of North America · 2023Review
- Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice.Blood advances · 2023Article
- STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia.Cell death discovery · 2023Article
- Molecular Characterization and Functional Analysis of Hypoxia-Responsive Factor Prolyl Hydroxylase Domain 2 in Mandarin Fish (Animals : an open access journal from MDPI · 2023Article
- Development of drugs targeting hypoxia-inducible factor against tumor cells with VHL mutation: Story of 127 years.Cancer science · 2023Review
- Von Hippel-Lindau disease: insights into oxygen sensing, protein degradation, and cancer.The Journal of clinical investigation · 2022Review
- Fabrication of Tβ4-Exosome-releasing artificial stem cells for myocardial infarction therapy by improving coronary collateralization.Bioactive materials · 2022Article
- Flexible and multifaceted: the plasticity of renin-expressing cells.Pflugers Archiv : European journal of physiology · 2022Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor (HIF), consisting of a labile alpha subunit and a stable beta subunit, is a master regulator of hypoxia-responsive mRNAs. HIF alpha undergoes oxygen-dependent prolyl hydroxylation, which marks it for polyubiquitination by a complex containing the von Hippel-Lindau protein (pVHL). Among the three Phd family members, Phd2 appears to be the primary HIF prolyl hydroxylase. Phd3 is induced by HIF and, based on findings from in vitro studies, may participate in a HIF-regulatory feedback loop. Here, we report that Phd3 loss exacerbates the HIF activation, hepatic steatosis, dilated cardiomyopathy, and premature mortality observed in mice lacking Phd2 alone and produces a closer phenocopy of the changes seen in mice lacking pVHL than the loss of Phd2 alone. Importantly, the degree to which Phd3 can compensate for Phd2 loss and the degree to which the combined loss of Phd2 and Phd3 resembles pVHL loss appear to differ for different HIF-responsive genes and in different tissues. These findings highlight that the responses of different HIF target genes to changes in prolyl hydroxylase activity differ, quantitatively and qualitatively, in vivo and have implications for the development of paralog-specific prolyl hydroxylase inhibitors as therapeutic agents.
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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.