ArticleBlood cells, molecules & diseases2010
Integrity of the prolyl hydroxylase domain protein 2:erythropoietin pathway in aging mice.
Article in Blood cells, molecules & diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- High-Altitude Andean H194R HIF2A Allele Is a Hypomorphic Allele.Molecular biology and evolution · 2023Article
- Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic β-Cell Function.Endocrinology · 2022Article
- The prolyl 4-hydroxylase inhibitor GSK360A decreases post-stroke brain injury and sensory, motor, and cognitive behavioral deficits.PloS one · 2017Article
- Identification of Small-Molecule PHD2 Zinc Finger Inhibitors that Activate Hypoxia Inducible Factor.Chembiochem : a European journal of chemical biology · 2016Article
- The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.Molecular and cellular biology · 2016Article
- Conditional Deletion of Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Gene Reveals Its Essential Role in Chondrocyte Function and Endochondral Bone Formation.Endocrinology · 2016Article
- Human high-altitude adaptation: forward genetics meets the HIF pathway.Genes & development · 2014Review
- Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism.Hypoxia (Auckland, N.Z.) · 2014Review
- The role of PHD2 mutations in the pathogenesis of erythrocytosis.Hypoxia (Auckland, N.Z.) · 2014Review
- A knock-in mouse model of human PHD2 gene-associated erythrocytosis establishes a haploinsufficiency mechanism.The Journal of biological chemistry · 2013Article
- Erythrocytosis and pulmonary hypertension in a mouse model of human HIF2A gain of function mutation.The Journal of biological chemistry · 2013Article
- Hypoxia-induced angiogenesis is delayed in aging mouse brain.Brain research · 2011Article
- Mouse knock-out of IOP1 protein reveals its essential role in mammalian cytosolic iron-sulfur protein biogenesis.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The central transcriptional response to hypoxia is mediated by the prolyl hydroxylase domain protein (PHD):hypoxia inducible factor (HIF) pathway. In this pathway, PHD prolyl hydroxylates and thereby negatively regulates the alpha-subunit of the transcription factor HIF (HIF-alpha). An important HIF target gene is that for erythropoietin (EPO), which controls red cell mass. Recent studies have identified PHD2 as the critical PHD isoform regulating the EPO gene. Other studies have shown that the inducibility of the HIF pathway diminishes as a function of age. Thus, an important question is whether the PHD2:EPO pathway is altered in the aging. Here, we employed a mouse line with a globally-inducible Phd2 conditional knockout allele to examine the integrity of the Phd2:Epo axis in young (six to eight months old) and aging (sixteen to twenty months old) mice. We find that acute global deletion of Phd2 results in a robust erythrocytosis in both young and aging mice, with both age groups showing marked extramedullary hematopoiesis in the spleen. Epo mRNA is dramatically upregulated in the kidney, but not in the liver, in both age groups. Conversely, other Hif targets, including Vegf, Pgk1, and Phd3 are upregulated in the liver but not in the kidney in both age groups. These findings have implications for targeting this pathway in the aging.
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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.