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Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD

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Abstract
Tissue hypoxia occurs when local oxygen demand exceeds oxygen supply. In chronic inflammatory conditions such as IBD, the increased oxygen demand by resident and gut-infiltrating immune cells coupled with vascular dysfunction brings about a marked reduction in mucosal oxygen concentrations. To counter the hypoxic challenge and ensure their survival, mucosal cells induce adaptive responses, including the activation of hypoxia-inducible factors (HIFs) and modulation of nuclear factor-kappa B (NF-kappa B). Both pathways are tightly regulated by oxygen-sensitive prolyl hydroxylases (PHDs), which therefore represent promising therapeutic targets for IBD. In this Review, we discuss the involvement of mucosal hypoxia and hypoxia-induced signalling in the pathogenesis of IBD and elaborate in detail on the role of HIFs, NF-kappa B and PHDs in different cell types during intestinal inflammation. We also provide an update on the development of PHD inhibitors and discuss their therapeutic potential in IBD.
Keywords
NF-KAPPA-B, INFLAMMATORY-BOWEL-DISEASE, INDUCIBLE FACTOR-I, NECROSIS-FACTOR-ALPHA, PROLYL HYDROXYLASE INHIBITION, HIF-DEPENDENT INDUCTION, DEXTRAN SULFATE SODIUM, LINKS INNATE IMMUNITY, NITRIC-OXIDE SYNTHASE, REGULATORY T-CELLS

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Chicago
Van Welden, Sophie, Andrew C Selfridge, and Pieter Hindryckx. 2017. “Intestinal Hypoxia and Hypoxia-induced Signalling as Therapeutic Targets for IBD.” Nature Reviews Gastroenterology & Hepatology 14 (10): 596–611.
APA
Van Welden, S., Selfridge, A. C., & Hindryckx, P. (2017). Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD. NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 14(10), 596–611.
Vancouver
1.
Van Welden S, Selfridge AC, Hindryckx P. Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD. NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY. 2017;14(10):596–611.
MLA
Van Welden, Sophie, Andrew C Selfridge, and Pieter Hindryckx. “Intestinal Hypoxia and Hypoxia-induced Signalling as Therapeutic Targets for IBD.” NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY 14.10 (2017): 596–611. Print.
@article{8540067,
  abstract     = {Tissue hypoxia occurs when local oxygen demand exceeds oxygen supply. In chronic inflammatory conditions such as IBD, the increased oxygen demand by resident and gut-infiltrating immune cells coupled with vascular dysfunction brings about a marked reduction in mucosal oxygen concentrations. To counter the hypoxic challenge and ensure their survival, mucosal cells induce adaptive responses, including the activation of hypoxia-inducible factors (HIFs) and modulation of nuclear factor-kappa B (NF-kappa B). Both pathways are tightly regulated by oxygen-sensitive prolyl hydroxylases (PHDs), which therefore represent promising therapeutic targets for IBD. In this Review, we discuss the involvement of mucosal hypoxia and hypoxia-induced signalling in the pathogenesis of IBD and elaborate in detail on the role of HIFs, NF-kappa B and PHDs in different cell types during intestinal inflammation. We also provide an update on the development of PHD inhibitors and discuss their therapeutic potential in IBD.},
  author       = {Van Welden, Sophie and Selfridge, Andrew C and Hindryckx, Pieter},
  issn         = {1759-5045},
  journal      = {NATURE REVIEWS GASTROENTEROLOGY \& HEPATOLOGY},
  language     = {eng},
  number       = {10},
  pages        = {596--611},
  title        = {Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD},
  url          = {http://dx.doi.org/10.1038/nrgastro.2017.101},
  volume       = {14},
  year         = {2017},
}

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