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Cited by 461Inflammatory Bowel DiseaseGut microbiota and healthCancer, Hypoxia, and Metabolism

Hypoxia: an alarm signal during intestinal inflammation

Open access
Colgan, Sean P., Taylor, Cormac T.·2010·Nature Reviews Gastroenterology & Hepatology
DOI 10.1038/nrgastro.2010.39PMC PMC4077542
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Abstract

Intestinal epithelial cells that line the mucosal surface of the gastrointestinal tract are positioned between an anaerobic lumen and a highly metabolic lamina propria. As a result of this unique anatomy, intestinal epithelial cells function within a steep physiologic oxygen gradient relative to other cell types. Furthermore, during active inflammatory disease such as IBD, metabolic shifts towards hypoxia are severe. Studies in vitro and in vivo have shown that the activation of hypoxia-inducible factor (HIF) serves as an alarm signal to promote the resolution of inflammation in various mouse models of disease. Amelioration of disease occurs, at least in part, through transcriptional upregulation of nonclassic epithelial barrier genes. There is much interest in harnessing hypoxia-inducible pathways, including stabilizing HIF directly or via inhibition of prolyl hydroxylase enzymes, for therapy of IBD. In this Review, we discuss the signaling pathways involved in the regulation of hypoxia and discuss how hypoxia may serve as an endogenous alarm signal for the presence of mucosal inflammatory disease. We also discuss the pros and cons of targeting these pathways to treat patients with IBD.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that hypoxia in the inflamed intestinal mucosa acts as an endogenous alarm signal, with HIF activation promoting resolution of inflammation and barrier protection in murine colitis models. It discusses PHD inhibitors as potential IBD therapies but cautions about hematocrit elevation and cancer risk.

Key findings

  • The intestinal mucosa normally exists in a steep oxygen gradient; 2-nitroimidazole dye studies in murine IBD models show physiologic hypoxia in normal colon and profoundly hypoxic or anoxic inflammatory lesions. The adult intestinal epithelium covers approximately 300 m² and absorbs at least 9 L of fluid daily; gut blood volume shifts from less than 5% during fasting to approximately 30% after a meal.
  • HIF-1 is induced in inflammatory lesions. Loss of epithelial HIF-1α resulted in a more severe colitic phenotype than wild-type animals, with increased weight loss, decreased colon length and increased epithelial permeability, whereas constitutively active intestinal epithelial HIF was protective; however, another study found epithelial HIF-based signaling can promote inflammation.
  • HIF-dependent barrier protection involves non-classical epithelial barrier genes, including mucins, intestinal trefoil factor, P-glycoprotein, CD73 and the adenosine A2B receptor, rather than tight junction proteins occludin or claudin. PHDs also regulate NF-κB via IKKβ hydroxylation.
  • PHD inhibitors DMOG and FG-4497 reduced symptoms in at least two mouse models of colitis (TNBS or DSS) and were well tolerated; high-dose FG-4497 (>60 mg/kg) with 5 daily intervals caused occasional intestinal vascular occlusion, likely from erythrocyte sludging, rectified by lowering the dose and decreasing the dosing interval. No trials have been initiated for the treatment of IBD.

Methods

  • Design: narrative review of hypoxia signaling in intestinal inflammation, synthesizing in vitro studies, murine disease models and patient-derived materials.
  • Main analysis: descriptive synthesis of HIF, PHD and NF-κB pathways and preclinical therapeutic studies of PHD inhibitors in colitis models; no systematic search or quantitative meta-analysis is reported.

Limitations

  • Stated: increased susceptibility to colitis after genetic deletion of intestinal epithelial HIF may be somewhat model-dependent and requires additional validation with PHD inhibitors before clinical studies can be implemented. The paper also cautions that HIF activators substantially elevate hematocrit; high-dose FG-4497 caused occasional vascular occlusion, and chronic HIF-1 and HIF-2 stabilization has been significantly associated with cancers, so safest use may be acute or short-term adjunct therapy.
  • Evident from the text: this is a narrative review without systematic search or quantitative synthesis, and therapeutic evidence is largely from murine colitis models; no IBD trials have been initiated.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/nrgastro.2010.39

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 48 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the authors' initial studies with murine colitis, high doses of FG-4497 (>60 mg/kg) with 5 daily intervals of dosing resulted in occasional vascular occlusion within the intestine.

    “In our initial studies with murine colitis, we observed that high doses of FG-4497 (>60 mg/kg) with 5 daily intervals of dosing resulted in occasional vascular occlusion within the intestine.”
    Quote in the paperSubstantial claim
  • Premisereasoning

    Intestinal epithelial cells function within a steep physiologic oxygen gradient relative to other cell types.

    “Intestinal epithelial cells that line the mucosal surface of the gastrointestinal tract are positioned between an anaerobic lumen and a highly metabolic lamina propria. As a result of this unique anatomy, intestinal epithelial cells function within a steep physiologic oxygen gradient relative to other cell types.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: There is a steep oxygen gradient from the anaerobic lumen of the intestine across the epithelium into the highly vascularized sub-epithelium.
  • Interpretationnone given

    Activation of HIF serves as an alarm signal for the resolution of inflammation in various murine disease models.

    “Studies in vitro and in vivo have shown that the activation of hypoxia-inducible factor (HIF) serves as an alarm signal for the resolution of inflammation in various murine disease models.”
    Quote in the paperSubstantial claim
  • Interpretationcitation

    Amelioration of disease occurs, at least in part, through transcriptional up-regulation of non-classical epithelial barrier genes.

    “Amelioration of disease occurs, at least in part, through transcriptional up-regulation of non-classical epithelial barrier genes.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [4] Furuta, G. T. et al. Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J. Exp. Med. 193, 1027–1034 (2001). source

      Not checked in the free run.

    • cites [20] Comerford, K. M. et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res. 62, 3387–3394 (2002).

      Not checked in the free run.

    • cites [21] Synnestvedt, K. et al. Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 (HIF-1) mediates permeability changes in intestinal epithelia. J. Clin. Invest. 110, 993–1002 (2002). source

      Not checked in the free run.

    • cites [22] Eltzschig, H. K. et al. Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors. J. Exp. Med. 198, 783–796 (2003). source

      Not checked in the free run.

  • Premisecitation

    During active inflammatory disease such as IBD, metabolic shifts toward hypoxia are severe.

    “Furthermore, during active inflammatory disease such as IBD, metabolic shifts toward hypoxia are severe.”
    • Also stated in: § Hypoxia and the immune response · plain
      “IBD is an interesting disease for studying the metabolic changes associated with inflammation, particularly the development of hypoxia within inflammatory lesions3.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Taylor, C. T. & Colgan, S. P. Hypoxia and gastrointestinal disease. J. Mol. Med. 85, 1295–1300 (2008). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. 5
  • May combine two claims. 18

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the authors' experience, both FG-4497 and DMOG can be delivered by multiple routes of administration (intraperitoneal, oral and intravenous), and both FG-4497 are absorbed orally with only a slight loss of efficacy compared to intraperitoneal administration.

    “In our experience, both FG-4497 and DMOG can be delivered by multiple routes of administration (intraperitoneal, oral and intravenous)., and both FG-4497 are absorbed orally with only a slight loss of efficacy compared to intraperitoneal administration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    This problem was rectified by lowering the dose and decreasing the interval of dosing.

    “This problem was rectified by lowering the dose and decreasing the interval of dosing26.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Robinson, A. et al. Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition. Gastroenterology 134, 145–155 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sites of mucosal inflammation are characterized by profound changes in tissue metabolism, including local depletion of nutrients, imbalances in tissue oxygen supply and demand, and generation of large quantities of reactive nitrogen and oxygen intermediates.

    “Sites of mucosal inflammation are characterized by profound changes in tissue metabolism, including local depletion of nutrients, imbalances in tissue oxygen supply and demand, and the generation of large quantities of reactive nitrogen and oxygen intermediates3.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Taylor, C. T. & Colgan, S. P. Hypoxia and gastrointestinal disease. J. Mol. Med. 85, 1295–1300 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The PMN oxidative burst is not hindered by even relatively low O2 (as low as 4.5% O2), so ROS can be generated in the relatively low O2 environments of inflamed intestinal mucosa.

    “Notably, the PMN oxidative burst is not hindered by even relatively low O2 (as low as 4.5% O2)8, which is important, since it means that ROS can be generated in the relatively low O2 environments of inflamed intestinal mucosa3.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Gabig, T. G., Bearman, S. I. & Babior, B. M. Effects of oxygen tension and pH on the respiratory burst of human neutrophils. Blood 53, 1133–1139 (1979). source

      Not checked in the free run.

    • cites [3] Taylor, C. T. & Colgan, S. P. Hypoxia and gastrointestinal disease. J. Mol. Med. 85, 1295–1300 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both the absorptive and barrier functions of the intestinal epithelium are regulated by the availability of O2.

    “Both the absorptive and barrier functions of the intestinal epithelium are regulated by the availability of O23.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Taylor, C. T. & Colgan, S. P. Hypoxia and gastrointestinal disease. J. Mol. Med. 85, 1295–1300 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intestinal epithelial cells seem uniquely resistant to hypoxia, and extremely low oxygenation within the normal intestinal epithelial barrier (physiologic hypoxia) may be a regulatory adaptation mechanism to the steep oxygen gradient.

    “In fact, studies comparing functional responses between epithelial cells from different tissues have revealed that intestinal epithelial cells seem to be uniquely resistant to hypoxia and that an extremely low level of oxygenation within the normal intestinal epithelial barrier (so-called “physiologic hypoxia”) may be a regulatory adaptation mechanism to the steep oxygen gradient4.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Furuta, G. T. et al. Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J. Exp. Med. 193, 1027–1034 (2001). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Hypoxia-regulated pathways are highly associated with IBD and contribute particularly to the resolution of ongoing inflammation.

    “Ongoing studies suggest that hypoxia-regulated pathways are highly associated with IBD and contribute particularly to the resolution of ongoing inflammation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    PMNs are primarily glycolytic cells, with few mitochondria and little energy produced from respiration.

    “It has long been known that PMNs are primarily glycolytic cells, with few mitochondria and little energy produced from respiration6.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Borregaard, N. & Herlin, T. Energy metabolism of human neutrophils during phagocytosis. J. Clin. Invest. 70, 550–557 (1982). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Loss of epithelial HIF-1α results in a more severe colitic phenotype than wild-type animals, with increased weight loss, decreased colon length and increased epithelial permeability, whereas constitutively active intestinal epithelial HIF is protective for these parameters.

    “Loss of epithelial HIF-1α resulted in a more severe colitic phenotype than wild-type animals, with increased weight loss, decreased colon length and increased epithelial permeability, whereas constitutively active intestinal epithelial HIF was protective for these parameters.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Karhausen, J. et al. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J. Clin. Invest. 114, 1098–1106 (2004). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inflammatory lesions in mouse models of IBD are profoundly hypoxic or even anoxic, similar to some large tumors, and penetrate deep into the mucosal tissue.

    “Second, the inflammatory lesions seen in these mouse models are profoundly hypoxic or even anoxic, similar to that seen in some large tumors, and penetrate deep into the mucosal tissue.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Evans, S. M. et al. Detection of hypoxia in human squamous cell carcinoma by EF5 binding. Cancer Res. 60, 2018–2024 (2000).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PMN and macrophage bacterial killing capacities are severely limited in the absence of HIF-1α, as HIF-1α is central to production of antimicrobial peptides and granule proteases.

    “In particular, these studies have shown that PMN and macrophage bacterial killing capacities are severely limited in the absence of HIF-1α, as HIF-1α is central to production of antimicrobial peptides and granule proteases.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Nizet, V. & Johnson, R. S. Interdependence of hypoxic and innate immune responses. Nat. Rev. Immunol. 9, 609–617 (2009). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Four HIF-hydroxylases termed PHD1-3 and FIH are important in the hypoxic regulation of the HIF pathway.

    “Four HIF-hydroxylases termed PHD1-3 and Functional Inhibitor of HIF (FIH) have been demonstrated to be important in the hypoxic regulation of the HIF pathway37.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Kaelin, W. G. Jr & Ratcliffe, P. J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell 30, 393–402 (2008). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NF-κB is thought to be largely protective in the intestinal epithelium via the inhibition of enterocyte apoptosis leading to enhanced intestinal barrier function.

    “Likewise, NF-κB is thought to be largely protective in the intestinal epithelium via the inhibition of enterocyte apoptosis leading to enhanced intestinal barrier function23.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Cummins, E. P. et al. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 134, 156–165 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    HIF-dependent pathways are more to do with overall tissue integrity, ranging from increased mucin production, including molecules that modify mucins such as intestinal trefoil factor, to xenobiotic clearance by P-glycoprotein, to nucleotide metabolism (by ecto-5′-nucleotidase and CD73) and nucleotide signaling through the adenosine A2B receptor.

    “Rather, the HIF-dependent pathways are more to do with overall tissue integrity, ranging from increased mucin production,31 including molecules that modify mucins, such as, intestinal trefoil factor4, to xenobiotic clearance by P-glycoprotein,20 to nucleotide metabolism (by ecto-5′-nucleotidase and CD73)21,22 and nucleotide signaling through the adenosine A2B receptor22.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [31] Louis, N. A. et al. Selective induction of mucin-3 by hypoxia in intestinal epithelia. J. Cell Biochem. 99, 1616–1627 (2006). source

      Not checked in the free run.

    • cites [4] Furuta, G. T. et al. Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J. Exp. Med. 193, 1027–1034 (2001). source

      Not checked in the free run.

    • cites [20] Comerford, K. M. et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res. 62, 3387–3394 (2002).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypoxia has been shown to activate NF-κB and this seems, at least in part, dependent on PHD-mediated hydroxylation of IKKβ.

    “Indeed, hypoxia has been shown to activate NF-κB and this seems, at least in part to be, to be dependent on PHD-mediated hydroxylation38,49 of IKKβ.38”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38] Cummins, E. P. et al. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc. Natl Acad. Sci. USA 103, 18154–18159 (2006). source

      Not checked in the free run.

    • cites [49] Cockman, M. E. et al. Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Proc. Natl Acad. Sci. USA 103, 14767–14772 (2006). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Intestinal epithelial cells can adapt to hypoxia and HIF may contribute to this.

    “However, the findings confirmed that intestinal epithelial cells can adapt to hypoxia and that HIF may contribute to this.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NF-κB has recently been reported to be regulated by HIF hydroxylases in a number of studies.

    “For example, NF-κB has recently been reported to be regulated by HIF hydroxylases in a number of studies37,44.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Kaelin, W. G. Jr & Ratcliffe, P. J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell 30, 393–402 (2008). source

      Not checked in the free run.

    • cites [44] Taylor, C. T. Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation. J. Physiol. 586, 4055–4059 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In these mouse models, the drugs were well tolerated with no significant adverse side effects.

    “In these mouse models, the drugs were well tolerated with no significant adverse side effects.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23] Cummins, E. P. et al. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 134, 156–165 (2008). source

      Not checked in the free run.

    • cites [26] Robinson, A. et al. Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition. Gastroenterology 134, 145–155 (2008). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Increased susceptibility to colitis following genetic deletion of intestinal epithelial HIF may be somewhat model-dependent and will require additional validation with PHD inhibitors before clinical studies can be implemented.

    “It is notable that the increased susceptibility to colitis following the genetic deletion of intestinal epithelial HIF may be somewhat model-dependent and will require additional validatation with PHD inhibitors before clinical studies can be implements.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Conditional deletion of the NF-κB pathway in intestinal epithelial cells in mice leads to an increased susceptibility to colitis, similar to that of mice expressing homozygous mutant HIF1α.

    “It is notable that conditional deletion of the NF-κB pathway in intestinal epithelial cells in mice leads to an increased susceptibility to colitis50, similar to that of the mice expressing homozygous mutant HIF1α13.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Zaph, C. et al. Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis. Nature 446, 552–556 (2007). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Epithelial NF-κB has a prominently protective role in colitis, probably through expression of anti-apoptotic genes in intestinal epithelial cells and through enhanced epithelial barrier function.

    “This implicates epithelial NF-κB in a prominently protective role in colitis, probably through the expression of anti-apoptotic genes in intestinal epithelial cells and through enhanced epithelial barrier function.”
    Quote in the paperSubstantial claim
21 of 21

  • The paper relies on this without support.

    Loss of epithelial barrier function with unrestricted flux of luminal antigens to the mucosal immune system underlies the pathology of IBD and results in hypoxia within the chronically inflamed mucosa, particularly within the epithelial cell layer.

    “Loss of epithelial barrier function with the resultant unrestricted flux of luminal antigens to the mucosal immune system underlies the pathology of IBD, and results in hypoxia within the chronically inflamed mucosa, particularly within the epithelial cell layer.”

  • The paper relies on this without support.

    When activated, PMN can consume up to 10 times more O2 than any other cell in the body.

    “When activated, it is estimated that PMN can consume up to 10 times more O2 than any other cell in the body.”

  • The paper relies on this without support.

    There is a steep oxygen gradient from the anaerobic lumen of the intestine across the epithelium into the highly vascularized sub-epithelium.

    “Notably, there is a steep oxygen gradient from the anaerobic lumen of the intestine across the epithelium into the highly vascularized sub-epithelium.”

  • The paper relies on this without support.

    Chronic HIF-1 and HIF-2 stabilization are significantly associated with a number of cancers.

    “As a second precautionary note, chronic HIF-1 and HIF-2 stabilization have been significantly associated with a number of cancers.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Prolyl hydroxylase is described as both stabilizing and degrading HIF

    Minor

    The abstract says the prolyl-hydroxylase enzyme stabilizes HIF, but the main text says these enzymes lead to HIF degradation and that inhibiting them stabilizes HIF.

1 of 1

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Related

Authors
Colgan, S. P., & Taylor, C. T.
Affiliations
  • University of Colorado Denver (US)
  • University College Dublin (IE)
Corresponding author
Colgan, Sean P.
ORCID
Venue
Nature Reviews Gastroenterology & Hepatology
Publisher
Springer Science and Business Media LLC
Published
2010-04-06
Volume
7
Issue
5
Pages
281-287
ISSN
  • 1759-5045 (ISSN-L)
  • 1759-5053
DOI
10.1038/nrgastro.2010.39
PMC
PMC4077542
OpenAlex
W2018782206
Cited by
461
References
63
Citations by year
2026: 22 · 2025: 25 · 2024: 28 · 2023: 26 · 2022: 28 · 2021: 35 · 2020: 20 · 2019: 31 · 2018: 32 · 2017: 33 · 2016: 38 · 2015: 37 · 2014: 31 · 2013: 29 · 2012: 21
FWCI
2.54
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Gastroenterology & Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Research Repository UCD (University College Dublin) (submittedVersion, cc-by-nc-nd)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-nd)
Funders
  • Crohn's and Colitis Foundation of America
  • Crohn's and Colitis Foundation
  • National Institutes of Health (DE016191, DK-50189, HL60569)
  • National Heart, Lung, and Blood Institute (R01HL060569, HL-60569)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK050189, R37DK050189, R29DK050189, DK-50189)
  • National Institute of Dental and Craniofacial Research (P50DE016191, DE 016191)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
hypoxia, intestinal inflammation, inflammatory bowel disease, hypoxia-inducible factor, HIF stabilization, prolyl hydroxylase inhibition, intestinal epithelial barrier, oxygen gradients, inflammation resolution, mucosal inflammation
MeSH terms
Animals, Hypoxia, Humans, Intestinal Mucosa, Inflammatory Bowel Diseases, Oxidative Stress, Hypoxia-Inducible Factor 1

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