5 years ago

Hypoxia-sensitive pathways in intestinal inflammation.

Cormac T Taylor, Eric Brown
Inflammatory bowel disease (IBD) is a common chronic intestinal disorder characterised by a loss of epithelial barrier function leading to the unregulated movement of luminal antigenic material into mucosal tissue with resultant inflammation. In IBD, multiple components of the inflammatory response lead to tissue hypoxia. Mucosal hypoxia leads to the inactivation of prolyl hydroxylase domain-containing (PHD) enzymes which in turn leads to the stabilization of the hypoxia-inducible factor (HIF) which induces the expression of barrier protective genes. Furthermore, pharmacologic hydroxylase inhibition has been shown to be protective in colitis, at least in part through enhancing intestinal epithelial barrier function through HIF-1-dependent barrier-protective gene expression. Therefore, targeting hypoxia-sensitive pathways represents a new and promising therapeutic approach in IBD. This article is protected by copyright. All rights reserved.

Publisher URL: http://doi.org/10.1113/JP274350

DOI: 10.1113/JP274350

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