Reactivation of hepatic EPO synthesis in mice after PHD loss
Open accessAbstract
The kidney controls erythropoietin production in adults, and the anemia that can accompany renal failure is a major medical problem. The liver controls erythropoietin production during fetal life but is silenced shortly after birth. Erythropoietin transcription is controlled by hypoxia-inducible factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3). Systemic PHD2 inactivation has been found to increase renal, but not hepatic, erythropoietin production. In contrast, we show here that simultaneous genetic inactivation of all three PHD paralogs in mice reactivates hepatic erythropoietin production and stimulates red blood synthesis, suggesting that pan-PHD inhibitory drugs might be useful for the treatment of anemia caused by chronic kidney disease.
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In adults, the liver retains the ability to produce EPO in response to moderate/severe hypoxia or pharmacologic HIF activation.
“However, in adults, the liver retains its ability to produce EPO in response to moderate/severe hypoxia or to pharmacologic HIF activation. 23–25”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [25]
Genetic or pharmacologic inactivation of all three PHDs is required to produce a strong and sustained erythropoietic response.
“Genetic or pharmacologic inactivation of all three PHDs, however, is required to produce a strong and sustained erythropoietic response.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [25]
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- Authors
- Minamishima, Y. A., & Kaelin, W. G.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Kaelin, William G.
- Venue
- Science
- Published
- 2010-07-23
- Volume
- 329
- Issue
- 5990
- Pages
- 407-407
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3668543
- OpenAlex
- W2035855731
- Cited by
- 163
- References
- 8
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 10 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 19 · 2014: 12 · 2013: 14 · 2012: 16
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA068490)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- erythropoietin, prolyl hydroxylase, PHD2, PHD1, PHD3, hypoxia-inducible factor, anemia of chronic kidney disease, chronic kidney disease, erythropoiesis, prolyl hydroxylase inhibitors
- MeSH terms
- Anemia, Animals, Erythropoiesis, Erythropoietin, Hematocrit, Kidney Failure, Chronic, Liver, Procollagen-Proline Dioxygenase, Transcription Factors, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia-Inducible Factor-Proline Dioxygenases
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