The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index.
The Hydroxylase Inhibitor Dimethyloxalylglycine Is Protective in a Murine Model of Colitis
Open accessAbstract
Background & aims Prolyl and asparaginyl hydroxylases are key oxygen-sensing enzymes that confer hypoxic sensitivity to transcriptional regulatory pathways including the hypoxia inducible factor 1 (HIF-1) and nuclear factor-kappaB (NF-kappaB). Knockout of either HIF-1 or (IKKbeta-dependent) NF-kappaB pathways in intestinal epithelial cells promotes inflammatory disease in murine models of colitis. Both HIF-1 and NF-kappaB pathways are repressed by the action of hydroxylases through the hydroxylation of key regulatory molecules.Methods In this study we have investigated the effects of the hydroxylase inhibitor dimethyloxalylglycine (DMOG) on Caco-2 intestinal epithelial cells in vitro and in a dextran sodium sulfate-induced model of murine colitis.Results DMOG induces both HIF-1 and NF-kappaB activity in cultured intestinal epithelial cells, and is profoundly protective in dextran-sodium sulfate colitis in a manner that is at least in part reflected by the development of an anti-apoptotic phenotype in intestinal epithelial cells, which we propose reduces epithelial barrier dysfunction.Conclusions These data show that hydroxylase inhibitors such as DMOG represent a new strategy for the treatment of inflammatory bowel disease.
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“and to limit inflammation in models of inflammatory bowel disease and LPS-induced shock [117–120].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [117]
In the citing paper
“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.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [23]
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“Indeed, these studies have shown that both DMOG and FG-4497 provide an overall beneficial influence on multiple parameters studied in chemically induced (trinitrobenzene sulfonic acid [TNBS] or dextran sodium sulfate [DSS] mouse models of colitis.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [23]
In the citing paper
“Within the gastrointestinal tract, the PHD inhibitors DMOG and FG-4497 have been used effectively to reduce symptoms in at least two mouse models of colitis23,26.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [23]
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“In these mouse models, the drugs were well tolerated with no significant adverse side effects.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [23]
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Cites
Nuclear factor-κB in cancer development and progression
Karin, M. (2006) · Nature · doi:10.1038/nature04870 · Cited by 3,519
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
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IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
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Okayasu, I., Hatakeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y., & NAKAYA, R. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90290-h · Cited by 2,408
Clinicopathologic study of dextran sulfate sodium experimental acute colitis
Shichijo, K., Matuu, M., Ikeda, Y., Naito, S., Ito, M., & Sekine, I. (1998) · The Japanese Journal of Pharmacology · doi:10.1016/s0021-5198(19)41298-5 · Cited by 1,945
Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis
Sartor, R. B. (2006) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep0528 · Cited by 1,806
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
The fundamental basis of inflammatory bowel disease
Strober, W., Fuss, I. J., & Mannon, P. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30587 · Cited by 1,337
Epithelial NEMO links innate immunity to chronic intestinal inflammation
Nenci, A., Becker, C., Wullaert, A., Gareus, R., Loo, G., Danese, S., Huth, M., Nikolaev, A., Neufert, C. F., Madison, B., et al. (2007) · Nature · doi:10.1038/nature05698 · Cited by 1,077
Cummins, E. P., Berra, E., Comerford, K. M., Ginouves, A., Fitzgerald, K. T., Seeballuck, F., Godson, C., Nielsen, J. E., Moynagh, P., Pouyssegur, J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602235103 · Cited by 788
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Hypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
“Treatment of wild-typemice with DMOG reduced the severity of chemical (Cummins et al., 2008) or bacterial (Hirota et al.”
BackgroundEltzschig, H. K., & Carmeliet, P. (2011) · New England Journal of Medicine · doi:10.1056/nejmra0910283 · Cited by 2,061
HIF transcription factors, inflammation, and immunity
Palazon, A., Goldrath, A. W., Nizet, V., & Johnson, R. S. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.008 · Cited by 1,195
Regulation of glycolysis by the hypoxia-inducible factor (HIF): Implications for cellular physiology
Kierans, S. J., & Taylor, C. T. (2021) · The Journal of Physiology · doi:10.1113/jp280572 · Cited by 1,015
“…inducing cell death in monocytes (Crifo et al. 2019), neutrophils (Manresa et al. 2019), and enhancing intestinal epithelial barrier function (Cummins et al. 2008), in pro-angiogenic responses via the HIF-dependent upregulation of vascular endothelial growth factor (VEGF), offering…”
BackgroundSelf-citationThe role of HIF in immunity and inflammation
McGettrick, A. F., & O’Neill, L. A. J. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.08.002 · Cited by 768
Metadata
- Authors
- Cummins, E. P., Seeballuck, F., Keely, S. J., Mangan, N. E., Callanan, J. J., Fallon, P. G., & Taylor, C. T.
- Affiliations
- University College Dublin (IE)
- Royal College of Surgeons in Ireland (IE)
- Trinity College Dublin (IE)
- Corresponding author
- Taylor, Cormac T.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 134
- Issue
- 1
- Pages
- 156-165.e1
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2005539293
- Cited by
- 407
- References
- 39
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 18 · 2023: 18 · 2022: 21 · 2021: 24 · 2020: 24 · 2019: 18 · 2018: 28 · 2017: 25 · 2016: 31 · 2015: 23 · 2014: 22 · 2013: 28 · 2012: 27
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board
- Science Foundation Ireland
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Microscopic Colitis
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- dimethyloxalylglycine, colitis, inflammatory bowel disease, HIF-1, NF-κB, prolyl hydroxylase, asparaginyl hydroxylase, intestinal epithelial cells, Caco-2 cells, DSS-induced colitis, apoptosis, epithelial barrier dysfunction, hypoxia
- MeSH terms
- Amino Acids, Dicarboxylic, Animals, Colitis, Disease Models, Animal, Enzyme Inhibitors, Female, Humans, Mixed Function Oxygenases, Mice, Inbred C57BL, NF-kappa B, Cell Culture Techniques, Caco-2 Cells, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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