Hypoxic regulation of erythropoiesis and iron metabolism
Open accessAbstract
The kidney is a highly sensitive oxygen sensor and plays a central role in mediating the hypoxic induction of red blood cell production. Efforts to understand the molecular basis of oxygen-regulated erythropoiesis have led to the identification of erythropoietin (EPO), which is essential for normal erythropoiesis and to the purification of hypoxia-inducible factor (HIF), the transcription factor that regulates EPO synthesis and mediates cellular adaptation to hypoxia. Recent insights into the molecular mechanisms that control and integrate cellular and systemic erythropoiesis-promoting hypoxia responses and their potential as a therapeutic target for the treatment of renal anemia are discussed in this review.
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A Red carpet for iron metabolism
Muckenthaler, M. U., Rivella, S., Hentze, M. W., & Galy, B. (2017) · Cell · doi:10.1016/j.cell.2016.12.034 · Cited by 1,319 · see citing works
Regulation of erythropoiesis by hypoxia-inducible factors
Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787 · see citing works
Self-citationRed blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells
Mairbäurl, H. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00332 · Cited by 482 · see citing works
Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis
Liu, Q., Davidoff, O., Niss, K., & Haase, V. H. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63924 · Cited by 328 · see citing works
Self-citationAn overview of molecular basis of iron metabolism regulation and the associated pathologies
Silva, B., & Faustino, P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.03.011 · Cited by 300 · see citing works
Tong, W.-H., Sourbier, C., Kovtunovych, G., Jeong, S. Y., Vira, M., Ghosh, M., Romero, V. V., Sougrat, R., Vaulont, S., Viollet, B., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.07.018 · Cited by 212 · see citing works
The pleiotropic effects of erythropoietin in infection and inflammation
Nairz, M., Sonnweber, T., Schroll, A., Theurl, I., & Weiss, G. (2012) · Microbes and Infection · doi:10.1016/j.micinf.2011.10.005 · Cited by 161 · see citing works
Iron in the Tumor Microenvironment-Connecting the Dots
Pfeifhofer-Obermair, C., Tymoszuk, P., Petzer, V., Weiss, G., & Nairz, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00549 · Cited by 151 · see citing works
Greene, C. J., Attwood, K., Sharma, N. J., Gross, K. W., Smith, G. J., Xu, B., & Kauffman, E. C. (2017) · Oncotarget · doi:10.18632/oncotarget.22323 · Cited by 87 · see citing works
Kurhaluk, N., & Tkaczenko, H. (2025) · Nutrients · doi:10.3390/nu17040665 · Cited by 62 · see citing works
Laitala, A., Aro, E., Walkinshaw, G., Mäki, J. M., Rossi, M., Heikkilä, M., Savolainen, E.-R., Arend, M., Kivirikko, K. I., Koivunen, P., et al. (2012) · Blood · doi:10.1182/blood-2012-07-441824 · Cited by 58 · see citing works
Treatment of erythropoietin deficiency in mice with systemically administered siRNA
Querbes, W., Bogorad, R. L., Moslehi, J., Wong, J., Chan, A. Y., Bulgakova, E., Kuchimanchi, S., Akinc, A., Fitzgerald, K., Koteliansky, V., et al. (2012) · Blood · doi:10.1182/blood-2012-04-423715 · Cited by 45 · see citing works
- Authors
- Haase, V. H.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Haase, Volker H.
- ORCID
- Haase, Volker H.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2010-07
- Volume
- 299
- Issue
- 1
- Pages
- F1-F13
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC2904169
- OpenAlex
- W2157705760
- Cited by
- 347
- References
- 174
- Citations by year
- 2026: 13 · 2025: 31 · 2024: 22 · 2023: 20 · 2022: 26 · 2021: 25 · 2020: 25 · 2019: 16 · 2018: 15 · 2017: 18 · 2016: 18 · 2015: 20 · 2014: 24 · 2013: 29 · 2012: 20
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080821, R01DK081646)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- hypoxia, erythropoiesis, iron metabolism, erythropoietin, hypoxia-inducible factor, oxygen sensing, kidney, anemia of chronic kidney disease, transcriptional regulation, therapeutic target
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Anemia, Animals, Hypoxia, Bone Marrow, Erythrocytes, Erythropoiesis, Erythropoietin, Gene Expression Regulation, Hematinics, Homeostasis, Humans, Iron, Kidney, Oxygen, Polycythemia, Procollagen-Proline Dioxygenase, Protein Processing, Post-Translational, Basic Helix-Loop-Helix Proteins, Von Hippel-Lindau Tumor Suppressor Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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