The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index.
The human side of hypoxia‐inducible factor
Open accessAbstract
Summary: When humans are exposed to hypoxia, systemic and intracellular changes operate together to minimise hypoxic injury and restore adequate oxygenation. Emerging evidence indicates that the hypoxia‐inducible factor (HIF) family of transcription factors plays a central regulatory role in these homeostatic changes at both the systemic and cellular levels. HIF was discovered through its action as the transcriptional activator of erythropoietin, and has subsequently been found to control intracellular hypoxic responses throughout the body. HIF is primarily regulated by specific prolyl hydroxylase‐domain enzymes (PHDs) that initiate its degradation via the von Hippel‐Lindau tumour suppressor protein (VHL). The oxygen and iron dependency of PHD activity accounts for regulation of the pathway by both cellular oxygen and iron status. Recent studies conducted in patients with rare genetic diseases have begun to uncover the wider importance of the PHD‐VHL‐HIF axis in systems‐level human biology. These studies indicate that, in addition to regulating erythropoiesis, the system plays an important role in cardiopulmonary regulation. This article reviews our current understanding of the importance of HIF in human systems‐level physiology, and is modelled around the classic physiological response to high‐altitude hypoxia.
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Cites
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
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Self-citationHepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
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Cited by
Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (2009) · Physiology · doi:10.1152/physiol.00045.2008 · Cited by 926
Hypoxia induces rapid changes to histone methylation and reprograms chromatin
Batie, M., Frost, J., Frost, M., Wilson, J. W., Schofield, P., & Rocha, S. (2019) · Science · doi:10.1126/science.aau5870 · Cited by 385
A Genome-Wide Search for Signals of High-Altitude Adaptation in Tibetans
Xu, S., Li, S., Yang, Y., Tan, J., Lou, H., Jin, W., Yang, L., Pan, X., Wang, J., Shen, Y., et al. (2011) · Molecular Biology and Evolution · doi:10.1093/molbev/msq277 · Cited by 331
Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease
Fraisl, P., Aragonés, J., & Carmeliet, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2761 · Cited by 326
Oxygen sensing and hypoxia signalling pathways in animals: The implications of physiology for cancer
Ratcliffe, P. J. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.251470 · Cited by 294
Self-citation
Metadata
- Authors
- Smith, T. G., Robbins, P. A., & Ratcliffe, P. J.
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2008-04-09
- Volume
- 141
- Issue
- 3
- Pages
- 325-334
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W1591222350
- Cited by
- 266
- References
- 98
- FWCI
- 10.37
- Type
- journal article
- Language
- en
- Open access
- bronze
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