title: Adenosine and hypoxia-inducible factor signaling in intestinal injury and recovery.
abstract: The gastrointestinal mucosa has proven to be an interesting tissue in which to investigate disease-related metabolism. In this review, we outline some of the evidence that implicates hypoxia-mediated adenosine signaling as an important signature within both healthy and diseased mucosa. Studies derived from cultured cell systems, animal models, and human patients have revealed that hypoxia is a significant component of the inflammatory microenvironment. These studies have revealed a prominent role for hypoxia-induced factor (HIF) and hypoxia signaling at several steps along the adenine nucleotide metabolism and adenosine receptor signaling pathways. Likewise, studies to date in animal models of intestinal inflammation have demonstrated an almost uniformly beneficial influence of HIF stabilization on disease outcomes. Ongoing studies to define potential similarities with and differences between innate and adaptive immune responses will continue to teach us important lessons about the complexity of the gastrointestinal tract. Such information has provided new insights into disease pathogenesis and, importantly, will provide insights into new therapeutic targets.
authors.affiliation: Departments of Medicine and Anesthesiology and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045, USA. Sean.Colgan@UCDenver.edu
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism / Q000502:physiology; D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018928:Immunity, Mucosal / Q000502:physiology; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D007410:Intestinal Diseases / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D051379:Mice; D009711:Nucleotides / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009711:Nucleotides; D018047:Receptors, Purinergic P1; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011393:Procollagen-Proline Dioxygenase; D015720:5'-Nucleotidase; D000241:Adenosine