Abstract
Cells sense and respond to hypoxia through the activity of the transcription
factor HIF (hypoxia-inducible factor) and its regulatory hydroxylases, the prolyl
hydroxylase domain enzymes (PHDs). Multiple isoforms of HIFs and PHDs
exist, and isoform-selective roles have been identified in the context of the
inflammatory environment, which is itself frequently hypoxic. Recent advances
in the field have highlighted the complexity of this system, particularly with
regards to the cell and context-specific activity of HIFs and PHDs. Because
novel therapeutic agents which regulate this pathway are nearing the clinic,
understanding the role of HIFs and PHDs in inflammation outcomes is an
essential step in avoiding off-target effects and, crucially, in developing new
anti-inflammatory strategies.
factor HIF (hypoxia-inducible factor) and its regulatory hydroxylases, the prolyl
hydroxylase domain enzymes (PHDs). Multiple isoforms of HIFs and PHDs
exist, and isoform-selective roles have been identified in the context of the
inflammatory environment, which is itself frequently hypoxic. Recent advances
in the field have highlighted the complexity of this system, particularly with
regards to the cell and context-specific activity of HIFs and PHDs. Because
novel therapeutic agents which regulate this pathway are nearing the clinic,
understanding the role of HIFs and PHDs in inflammation outcomes is an
essential step in avoiding off-target effects and, crucially, in developing new
anti-inflammatory strategies.
| Original language | English |
|---|---|
| Journal | Trends in Molecular Medicine |
| DOIs | |
| Publication status | Published - 1 Nov 2018 |