ArticleMolecular and cellular biology2008
Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 187 citations in OpenAlex.
- Inactivation of the PHD3-FOXO3 axis blunts the type I interferon response in microglia and ameliorates Alzheimer's disease progression.Science advances · 2025Article
- 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 factors and essential hypertension: narrative review of experimental and clinical data.Pharmacological reports : PR · 2023Review
- Review
- HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics.Frontiers in endocrinology · 2023Review
- Deficiency of myeloid PHD proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signalling.Cardiovascular research · 2022Article
- Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic β-Cell Function.Endocrinology · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Developmental role of PHD2 in the pathogenesis of pseudohypoxic pheochromocytoma.Endocrine-related cancer · 2021Article
- Prolyl-4-hydroxylase 3 maintains β cell glucose metabolism during fatty acid excess in mice.JCI insight · 2021Article
- Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
- Hypoxia Inducible Factors as Central Players in the Pathogenesis and Pathophysiology of Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2021Review
- Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease.Frontiers in immunology · 2021Review
- Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.International journal of molecular sciences · 2020Review
- The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.Islets · 2020Review
- Hypoxia in the Initiation and Progression of Neuroblastoma Tumours.International journal of molecular sciences · 2019Review
- Leigh Syndrome Mouse Model Can Be Rescued by Interventions that Normalize Brain Hyperoxia, but Not HIF Activation.Cell metabolism · 2019Article
- Update on mutations in the HIF: EPO pathway and their role in erythrocytosis.Blood reviews · 2019Review
- EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
Abstract
Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3(-/-) mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3(-/-) mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3(-/-) mice with HIF-1a(+/-) and HIF-2a(+/-) mice demonstrated an interaction with HIF-2alpha but not HIF-1alpha, supporting the nonredundant involvement of a PHD3-HIF-2alpha pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3(-/-) mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the role of PHD3 in sympathoadrenal development extends beyond simple control of cell survival and organ mass, with functional PHD3 being required for proper anatomical and physiological integrity of the system. Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoadrenal functions, such as blood pressure regulation.
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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.