Hypoxia-inducible Factors in Physiology and Medicine

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Feb 7

PMID 22304911

Citations 1577

Authors

Gregg L Semenza

Affiliations

Soon will be listed here.

Abstract

Oxygen homeostasis represents an organizing principle for understanding metazoan evolution, development, physiology, and pathobiology. The hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis in all metazoan species. Rapid progress is being made in elucidating homeostatic roles of HIFs in many physiological systems, determining pathological consequences of HIF dysregulation in chronic diseases, and investigating potential targeting of HIFs for therapeutic purposes.

Citing Articles

Redefining the role of hypoxia-inducible factors (HIFs) in oxygen homeostasis.

Arias C, Acosta F, Bertocchini F, Fernandez-Arias C Commun Biol. 2025; 8(1):446.

PMID: 40089642 DOI: 10.1038/s42003-025-07896-1.

Prognostic significance and immune microenvironment infiltration patterns of hypoxia and endoplasmic reticulum stress-related genes in gastric cancer.

Li L, Liang Y, Xu W Front Oncol. 2025; 15:1542740.

PMID: 40061897 PMC: 11885130. DOI: 10.3389/fonc.2025.1542740.

Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.

Espin R, Medina-Jover F, Siguenza-Andrade J, Farran-Matas S, Mateo F, Figueras A NAR Cancer. 2025; 7(1):zcaf007.

PMID: 40061566 PMC: 11886861. DOI: 10.1093/narcan/zcaf007.

EPAS1 induction drives myocardial degeneration in desmoplakin-cardiomyopathy.

Kyriakopoulou E, van Kampen S, Wehrens M, Han S, de Ruiter H, Monshouwer-Kloots J iScience. 2025; 28(3):111895.

PMID: 40034852 PMC: 11872638. DOI: 10.1016/j.isci.2025.111895.

The Two Faces of Reactive Oxygen Species in Cancer.

Reczek C, Chandel N Annu Rev Cancer Biol. 2025; 1:79-98.

PMID: 40034143 PMC: 11875389. DOI: 10.1146/annurev-cancerbio-041916-065808.

References

Chandel N, Maltepe E, GOLDWASSER E, Mathieu C, Simon M, Schumacker P . Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A. 1998; 95(20):11715-20. PMC: 21706. DOI: 10.1073/pnas.95.20.11715. View

Dang E, Barbi J, Yang H, Jinasena D, Yu H, Zheng Y . Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011; 146(5):772-84. PMC: 3387678. DOI: 10.1016/j.cell.2011.07.033. View

Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo Z, Pool J . Sequencing of 50 human exomes reveals adaptation to high altitude. Science. 2010; 329(5987):75-8. PMC: 3711608. DOI: 10.1126/science.1190371. View

Suda T, Takubo K, Semenza G . Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell. 2011; 9(4):298-310. DOI: 10.1016/j.stem.2011.09.010. View

Ebos J, Lee C, Cruz-Munoz W, Bjarnason G, Christensen J, Kerbel R . Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009; 15(3):232-9. PMC: 4540346. DOI: 10.1016/j.ccr.2009.01.021. View

Chan D, Giaccia A . Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev. 2007; 26(2):333-9. DOI: 10.1007/s10555-007-9063-1. View

Zinkernagel A, Johnson R, Nizet V . Hypoxia inducible factor (HIF) function in innate immunity and infection. J Mol Med (Berl). 2007; 85(12):1339-46. DOI: 10.1007/s00109-007-0282-2. View

Mahon P, Hirota K, Semenza G . FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 2001; 15(20):2675-86. PMC: 312814. DOI: 10.1101/gad.924501. View

Jiang X, Khan M, Tian W, Beilke J, Natarajan R, Kosek J . Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection. J Clin Invest. 2011; 121(6):2336-49. PMC: 3104770. DOI: 10.1172/JCI46192. View

10.

Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouyssegur J . Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009; 29(10):2570-81. PMC: 2682037. DOI: 10.1128/MCB.00166-09. View

11.

Hirota S, Fines K, Ng J, Traboulsi D, Lee J, Ihara E . Hypoxia-inducible factor signaling provides protection in Clostridium difficile-induced intestinal injury. Gastroenterology. 2010; 139(1):259-69.e3. PMC: 3063899. DOI: 10.1053/j.gastro.2010.03.045. View

12.

Yun Z, Maecker H, Johnson R, Giaccia A . Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev Cell. 2002; 2(3):331-41. DOI: 10.1016/s1534-5807(02)00131-4. View

13.

Vaupel P, Mayer A, Hockel M . Tumor hypoxia and malignant progression. Methods Enzymol. 2004; 381:335-54. DOI: 10.1016/S0076-6879(04)81023-1. View

14.

Huang L, Bindra R, Glazer P, Harris A . Hypoxia-induced genetic instability--a calculated mechanism underlying tumor progression. J Mol Med (Berl). 2006; 85(2):139-48. DOI: 10.1007/s00109-006-0133-6. View

15.

Peng J, Zhang L, Drysdale L, Fong G . The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc Natl Acad Sci U S A. 2000; 97(15):8386-91. PMC: 26957. DOI: 10.1073/pnas.140087397. View

16.

Wang G, Jiang B, Rue E, Semenza G . Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995; 92(12):5510-4. PMC: 41725. DOI: 10.1073/pnas.92.12.5510. View

17.

Sarkar K, Fox-Talbot K, Steenbergen C, Bosch-Marce M, Semenza G . Adenoviral transfer of HIF-1alpha enhances vascular responses to critical limb ischemia in diabetic mice. Proc Natl Acad Sci U S A. 2009; 106(44):18769-74. PMC: 2774037. DOI: 10.1073/pnas.0910561106. View

18.

Wilkes D . Chronic lung allograft rejection and airway microvasculature: is HIF-1 the missing link?. J Clin Invest. 2011; 121(6):2155-7. PMC: 3104786. DOI: 10.1172/JCI58329. View

19.

Scortegagna M, Ding K, Oktay Y, Gaur A, Thurmond F, Yan L . Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1-/- mice. Nat Genet. 2003; 35(4):331-40. DOI: 10.1038/ng1266. View

20.

Yuan G, Khan S, Luo W, Nanduri J, Semenza G, Prabhakar N . Hypoxia-inducible factor 1 mediates increased expression of NADPH oxidase-2 in response to intermittent hypoxia. J Cell Physiol. 2011; 226(11):2925-33. PMC: 4695992. DOI: 10.1002/jcp.22640. View