REVIEW

Hypoxia inducible factor (HIF) in rheumatology: low O₂! See what HIF can do!

T Gaber¹, R Dziurla¹, R Tripmacher¹, G R Burmester², F Buttgereit¹

¹ Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University, and Deutsches Rheuma-Forschungszentrum Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
² Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University, Schumannstrasse 20/21, 10117 Berlin, Germany

Correspondence to:
Professor F Buttgereit
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstrasse 20/21, 10117 Berlin, Germany; frank.buttgereit{at}charite.de

Maintenance of oxygen homoeostasis is the basic principle in cell proliferation, differentiation, survival, and function in all higher organisms. The transcription factor, HIF (hypoxia inducible factor) has a central role in oxygen homoeostasis, and is indispensably linked to energy metabolism. Abnormally reduced oxygen concentrations leading to dysfunctional cell metabolism are found in rheumatoid arthritis and hence, knowledge of the molecular adaptive responses to hypoxia and the involvement of HIF in the pathogenesis of RA are interesting.

Abbreviations: AIA, adjuvant induced arthritis; ARNT, aryl hydrocarbon receptor nuclear translocator; bHLH, basic helix-loop-helix; CIA, collagen induced arthritis; COX-2, cyclo-oxygenase-2; CTAD, C-terminal transactivation domain; CTL, cytotoxic T lymphocyte; EC, endothelial cells; EPO, erythropoietin; FIH, factor inhibiting HIF-1; HIF, hypoxia inducible factor; HSP, heat shock protein; IL, interleukin; MAPK, mitogen activated protein kinase; MMP, matrix metalloproteinase; ODD, oxygen dependent degradation domain; PHD, prolyl hydroxylase domain-containing protein; PI3K, phosphatidylinositol 3-kinase; pVHL, von Hippel-Lindau tumour suppressor protein; RA, rheumatoid arthritis; ROS/RNS, reactive oxygen and nitrogen species; SDF-1, stromal cell derived factor 1; TNF, tumour necrosis factor ; VEGF, vascular endothelial growth factor

Keywords: energy metabolism; hypoxia; hypoxia inducible factor; oxygen homoeostasis; rheumatoid arthritis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• NONOMURA, Y., MIZOGUCHI, F., SUZUKI, A., NANKI, T., KATO, H., MIYASAKA, N., KOHSAKA, H. (2009). Hypoxia-induced Abrogation of Contact-dependent Inhibition of Rheumatoid Arthritis Synovial Fibroblast Proliferation. The Journal of Rheumatology 36: 698-705 [Abstract] [Full Text]  
• Moon, J.-O., Welch, T. P., Gonzalez, F. J., Copple, B. L. (2009). Reduced liver fibrosis in hypoxia-inducible factor-1{alpha}-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol. 296: G582-G592 [Abstract] [Full Text]  
• Ahn, J. K., Koh, E.-M., Cha, H.-S., Lee, Y. S., Kim, J., Bae, E.-K., Ahn, K.-S. (2008). Role of hypoxia-inducible factor-1{alpha} in hypoxia-induced expressions of IL-8, MMP-1 and MMP-3 in rheumatoid fibroblast-like synoviocytes. Rheumatology (Oxford) 47: 834-839 [Abstract] [Full Text]