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- Title
Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases.
- Authors
Eltzschig, Holger K.; Bratton, Donna L.; Colgan, Sean P.
- Abstract
Hypoxia-inducible factors (HIFs) are stabilized during adverse inflammatory processes associated with disorders such as inflammatory bowel disease, pathogen infection and acute lung injury, as well as during ischaemia-reperfusion injury. HIF stabilization and hypoxia-induced changes in gene expression have a profound impact on the inflamed tissue microenvironment and on disease outcomes. Although the mechanism that initiates HIF stabilization may vary, the final molecular steps that control HIF stabilization converge on a set of oxygen-sensing prolyl hydroxylases (PHDs) that mark HIFs for proteasomal degradation. PHDs are therefore promising therapeutic targets. In this Review, we discuss the emerging potential and associated challenges of targeting the PHD-HIF pathway for the treatment of inflammatory and ischaemic diseases.
- Subjects
HYPOXIA-inducible factors; INFLAMMATION treatment; ISCHEMIA treatment; TREATMENT of reperfusion injuries; TRANSCRIPTION factors; GENE expression
- Publication
Nature Reviews Drug Discovery, 2014, Vol 13, Issue 11, p852
- ISSN
1474-1776
- Publication type
Article
- DOI
10.1038/nrd4422