医学
缺氧诱导因子
信号通路
炎症性肠病
缺血
疾病
生物信息学
癌症研究
炎症
缺氧(环境)
免疫学
药理学
生物
基因
受体
内科学
化学
氧气
生物化学
有机化学
作者
Holger K. Eltzschig,Donna L. Bratton,Sean P. Colgan
摘要
Hypoxia-inducible factors (HIFs) have important roles in ischaemic and inflammatory diseases and strategies aimed at therapeutically modulating hypoxia signalling pathways are gaining considerable attention. Here, Eltzschig and colleagues focus on a set of oxygen-sensing prolyl hydroxylases — which are responsible for marking HIFs for proteasomal degradation — and assess their emerging potential as therapeutic targets. 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.
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