ArticleBlood2008
Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
What it found
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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.
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
143 citing papers in PubMed, 260 citations in OpenAlex.
- Trial
- Hypoxia Inducible Factor-2 Alpha and Prolinhydroxylase 2 Polymorphisms in Patients with Acute Respiratory Distress Syndrome (ARDS).International journal of molecular sciences · 2017Trial
- Alterations of Gene Expression and Signaling Pathway Activity in Venous Smooth Muscle Cells After Uremic Serum Exposure.International journal of molecular sciences · 2026Article
- Distinct HIF1α and HIF2α functions control skeletal muscle metabolism and erythropoiesis.The Journal of clinical investigation · 2026Article
- Ipriflavone FromMedComm · 2026Article
- IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin.PLoS biology · 2025Article
- Article
- Review
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- Hypoxia Inducible Factor pathway proteins in high-altitude mammals.Trends in biochemical sciences · 2024Review
- Hypoxia and the Hypoxia-Inducible Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Desidustat: a novel PHD inhibitor for the treatment of CKD-induced anemia.Frontiers in nephrology · 2024Review
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- Article
- Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.Frontiers in pharmacology · 2023Review
- Lack of Skeletal Effects in Mice with Targeted Disruptionof Prolyl Hydroxylase Domain 1 (Life (Basel, Switzerland) · 2022Article
- Renal hypoxia-HIF-PHD-EPO signaling in transition metal nephrotoxicity: friend or foe?Archives of toxicology · 2022Review
- Neurogenic and pericytic plasticity of conditionally immortalized cells derived from renal erythropoietin-producing cells.Journal of cellular physiology · 2022Article
- Effects of PHD and HSP90 on erythropoietin production in yak (Bos grunniens) renal interstitial fibroblast-like cells under hypoxia.Journal of molecular histology · 2022Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Polycythemia is often associated with erythropoietin (EPO) overexpression and defective oxygen sensing. In normal cells, intracellular oxygen concentrations are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins, which tag hypoxia-inducible factor (HIF) alpha subunits for polyubiquitination and proteasomal degradation by oxygen-dependent prolyl hydroxylation. Here we show that different PHD isoforms differentially regulate HIF-alpha stability in the adult liver and kidney and suppress Epo expression and erythropoiesis through distinct mechanisms. Although Phd1(-/-) or Phd3(-/-) mice had no apparent defects, double knockout of Phd1 and Phd3 led to moderate erythrocytosis. HIF-2alpha, which is known to activate Epo expression, accumulated in the liver. In adult mice deficient for PHD2, the prototypic Epo transcriptional activator HIF-1alpha accumulated in both the kidney and liver. Elevated HIF-1alpha levels were associated with dramatically increased concentrations of both Epo mRNA in the kidney and Epo protein in the serum, which led to severe erythrocytosis. In contrast, heterozygous mutation of Phd2 had no detectable effects on blood homeostasis. These findings suggest that PHD1/3 double deficiency leads to erythrocytosis partly by activating the hepatic HIF-2alpha/Epo pathway, whereas PHD2 deficiency leads to erythrocytosis by activating the renal Epo pathway.
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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.