Hydroxylase Inhibition Abrogates TNF-α–Induced Intestinal Epithelial Damage by Hypoxia-Inducible Factor-1–Dependent Repression of FADD
Open accessAbstract
Hydroxylase inhibitors stabilize hypoxia-inducible factor-1 (HIF-1), which has barrier-protective activity in the gut. Because the inflammatory cytokine TNF-α contributes to inflammatory bowel disease in part by compromising intestinal epithelial barrier integrity, hydroxylase inhibition may have beneficial effects in TNF-α–induced intestinal epithelial damage. The hydroxylase inhibitor dimethyloxalylglycin (DMOG) was tested in a murine model of TNF-α–driven chronic terminal ileitis. DMOG-treated mice experienced clinical benefit and showed clear attenuation of chronic intestinal inflammation compared with that of vehicle-treated littermates. Additional in vivo and in vitro experiments revealed that DMOG rapidly restored terminal ileal barrier function, at least in part through prevention of TNF-α–induced intestinal epithelial cell apoptosis. Subsequent transcriptional studies indicated that DMOG repressed Fas-associated death domain protein (FADD), a critical adaptor molecule in TNFR-1-mediated apoptosis, in an HIF-1α–dependent manner. Loss of this FADD repression by HIF-1α-targeting small interfering RNA significantly diminished the antiapoptotic action of DMOG. Additional molecular studies led to the discovery of a previously unappreciated HIF-1 binding site in the FADD promoter, which controls repression of FADD during hypoxia. As such, the results reported in this study allowed the identification of an innate mechanism that protects intestinal epithelial cells during (inflammatory) hypoxia, by direct modulation of death receptor signaling. Hydroxylase inhibition could represent a promising alternative treatment strategy for hypoxic inflammatory diseases, including inflammatory bowel disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
HIF activators elicit an M2-like macrophage phenotype.
“HIF activators appear capable of triggering multiple tissue protective pathways that protect epithelial cells from apoptosis, elicit an M2-like macrophage phenotype, and induce IL-10 production in B cells [119, 120].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [119]
HIF activators induce IL-10 production in B cells.
“HIF activators appear capable of triggering multiple tissue protective pathways that protect epithelial cells from apoptosis, elicit an M2-like macrophage phenotype, and induce IL-10 production in B cells [119, 120].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [119]
HIF activators limit inflammation in models of inflammatory bowel disease and LPS-induced shock.
“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 [119]
HIF activators protect epithelial cells from apoptosis.
“HIF activators appear capable of triggering multiple tissue protective pathways that protect epithelial cells from apoptosis, elicit an M2-like macrophage phenotype, and induce IL-10 production in B cells [119, 120].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [119]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
the NIDDK IBD Genetics Consortium, Barrett, J. C., the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Hansoul, S., Nicolae, D. L., Cho, J. H., Duerr, R. H., Rioux, J. D., Brant, S. R., et al. (2008) · Nature Genetics · doi:10.1038/ng.175 · Cited by 2,593 · see citing works
Self-citation(1999) · PubMed · Cited by 2,204 · see citing works
TNF-R1 Signaling: A Beautiful Pathway
Chen, G., & Goeddel, D. V. (2002) · Science · doi:10.1126/science.1071924 · Cited by 1,930 · see citing works
General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4304 · Cited by 1,468 · see citing works
Impaired On/Off Regulation of TNF Biosynthesis in Mice Lacking TNF AU-Rich Elements
Kontoyiannis, D. L., Pasparakis, M., Pizarro, T. T., Cominelli, F., & Kollias, G. A. (1999) · Immunity · doi:10.1016/s1074-7613(00)80038-2 · Cited by 1,329 · see citing works
Mazzone, M., Dettori, D., de Oliveira, R. L., Loges, S., Schmidt, T., Jonckx, B., Tian, Y.-M., Lanahan, A. A., Pollard, P. J., de Almodóvar, C. R., et al. (2009) · Cell · doi:10.1016/j.cell.2009.01.020 · Cited by 803 · see citing works
Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis
Karhausen, J., Furuta, G. T., Tomaszewski, J. E., Johnson, R. S., Colgan, S. P., & Haase, V. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421086 · Cited by 655 · see citing works
Death receptor signal transducers: nodes of coordination in immune signaling networks
Wilson, N., Dixit, V., & Ashkenazi, A. (2009) · Nature Immunology · doi:10.1038/ni.1714 · Cited by 569 · see citing works
Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity
Ukena, S. N., Singh, A., Dringenberg, U., Engelhardt, R., Seidler, U., Hansen, W., Bleich, A., Bruder, D., Franzke, A., Rogler, G., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001308 · Cited by 482 · see citing works
Furuta, G. T., Turner, J. R., Taylor, C. T., Hershberg, R. M., Comerford, K., Narravula, S., Podolsky, D. K., & Colgan, S. P. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.9.1027 · Cited by 449 · see citing works
The Hydroxylase Inhibitor Dimethyloxalylglycine Is Protective in a Murine Model of Colitis
Cummins, E. P., Seeballuck, F., Keely, S. J., Mangan, N. E., Callanan, J. J., Fallon, P. G., & Taylor, C. T. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.10.012 · Cited by 407 · see citing works
Hypoxia-inducible factor–dependent induction of netrin-1 dampens inflammation caused by hypoxia
Rosenberger, P., Schwab, J. M., Mirakaj, V., Masekowsky, E., Mager, A., Morote–Garcia, J. C., Unertl, K. E., & Eltzschig, H. K. (2009) · Nature Immunology · doi:10.1038/ni.1683 · Cited by 406 · see citing works
Schmitz, H., Fromm, M., Bentzel, C. J., Scholz, P., Detjen, K. M., Mankertz, J., Bode, H., Epple, H., Riecken, E., & Schulzke, J. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.1.137 · Cited by 375 · see citing works
Mucosal Protection by Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibition
Robinson, A., Keely, S., Karhausen, J., Gerich, M. E., Furuta, G. T., & Colgan, S. P. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.09.033 · Cited by 368 · see citing works
Interdependent roles for hypoxia inducible factor and nuclear factor‐κB in hypoxic inflammation
Taylor, C. T. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.157669 · Cited by 354 · see citing works
Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease
Fraisl, P., Aragonés, J., & Carmeliet, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2761 · Cited by 326 · see citing works
Ikeda, H., Suzuki, Y., Suzuki, M., Koike, M., Tamura, J., Tong, J., Nomura, M., & Itoh, G. (1998) · Gut · doi:10.1136/gut.42.4.530 · Cited by 315 · see citing works
Hypoxia and gastrointestinal disease
Taylor, C. T., & Colgan, S. P. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0277-z · Cited by 313 · see citing works
Zeißig, S., Bojarski, C., Buergel, N., Mankertz, J., Zeitz, M., Fromm, M., & Schulzke, J. D. (2004) · Gut · doi:10.1136/gut.2003.036632 · Cited by 305 · see citing works
Reimund, J., Wittersheim, C., Dumont, S., Muller, C. D., Kenney, J. S., Baumann, R., Poindron, P., & Duclos, B. (1996) · Gut · doi:10.1136/gut.39.5.684 · Cited by 297 · see citing works
Irvine, E. J., & Marshall, J. K. (2000) · Gastroenterology · doi:10.1053/gast.2000.20231 · Cited by 286 · see citing works
Varfolomeev, E. E., Maecker, H. L., Sharp, D. A., Lawrence, D. A., Renz, M. E., Vucic, D., & Ashkenazi, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509560200 · Cited by 278 · see citing works
Leaks in the epithelial barrier caused by spontaneous and TNF‐α‐induced single‐cell apoptosis
Gitter, A. H., Bendfeldt, K., Schulzke, J.-D., & Fromm, M. (2000) · The FASEB Journal · doi:10.1096/fj.99-0898com · Cited by 250 · see citing works
Narravula, S., & Colgan, S. P. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7543 · Cited by 219 · see citing works
Hypoxia inducible factor 1α and 2α overexpression in inflammatory bowel disease
Giatromanolaki, A. N., Sivridis, E., Maltezos, E., Papazoglou, D., Simopoulos, C., Gatter, K. C., Harris, A. L., & Koukourakis, M. I. (2003) · Journal of Clinical Pathology · doi:10.1136/jcp.56.3.209 · Cited by 209 · see citing works
Tambuwala, M. M., Cummins, E. P., Lenihan, C. R., Kiss, J., Stauch, M., Scholz, C. C., Fraisl, P., Lasitschka, F., Mollenhauer, M., Saunders, S. P., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.068 · Cited by 200 · see citing works
Marini, M., Bamias, G., Rivera–Nieves, J., Moskaluk, C. A., Hoang, S. B., Ross, W. G., Pizarro, T. T., & Cominelli, F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432897100 · Cited by 198 · see citing works
Disrupted Barrier Function through Epithelial Cell Apoptosis
Schulzke, J.-D., Bojarski, C., Zeißig, S., HELLER, F., Gitter, A. H., & Fromm, M. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1326.027 · Cited by 190 · see citing works
Taylor, C. T., Dzus, A. L., & Colgan, S. P. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70579-7 · Cited by 188 · see citing works
Morote–Garcia, J. C., Rosenberger, P., Nivillac, N. M. I., Coe, I. R., & Eltzschig, H. K. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.10.037 · Cited by 183 · see citing works
Hypoxia inducible factor 1 (HIF-1) and cardioprotection
Tekin, D., Dursun, A. D., & Xi, L. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.132 · Cited by 177 · see citing works
Increased gut permeability in Crohn’s disease: is TNF the link?
Gibson, P. R. (2004) · Gut · doi:10.1136/gut.2004.047092 · Cited by 152 · see citing works
Selective induction of mucin‐3 by hypoxia in intestinal epithelia
Louis, N. A., Hamilton, K. E., Canny, G., Shekels, L. L., Ho, S. B., & Colgan, S. P. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20947 · Cited by 144 · see citing works
Implication of TNF-Related Apoptosis-Inducing Ligand in Inflammatory Intestinal Epithelial Lesions
Bègue, B., Wajant, H., Bambou, J., Dubuquoy, L., Siegmund, D., Beaulieu, J., Canioni, D., Berrebi, D. D., Brousse, N., Desreumaux, P., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.022 · Cited by 135 · see citing works
Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney
Song, Y. R., You, S. J., Lee, Y.-M., Chin, H. J., Chae, D., Oh, Y. K., Joo, K. W., Han, J. S., & Na, K. Y. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp454 · Cited by 134 · see citing works
Primary Cultures of Fully Differentiated and Pure Human Intestinal Epithelial Cells
Perreault, N., & Beaulieu, J. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4221 · Cited by 132 · see citing works
Hua, Z. C., Sohn, S. J., Kang, C., Cado, D., & Winoto, A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00083-9 · Cited by 119 · see citing works
Zhang, J., & Winoto, A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.2756 · Cited by 118 · see citing works
Death Effector Domain-Containing Proteins
Valmiki, M. G., & Ramos, J. W. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8489-0 · Cited by 114 · see citing works
Animal Models of Inflammatory Bowel Disease: An Overview
Hoffmann, J. C., Pawlowski, N. N., Kühl, A. A., Höhne, W., & Zeitz, M. (2002) · Pathobiology · doi:10.1159/000068143 · Cited by 109 · see citing works
Prolyl Hydroxylase Domain Inhibitors: A Route to HIF Activation and Neuroprotection
Harten, S. K., Ashcroft, M. A., & Maxwell, P. H. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2870 · Cited by 99 · see citing works
Zheng, W. S., Kuhlicke, J., Jäckel, K., Eltzschig, H. K., Singh, A. K., Sjöblom, M., Riederer, B., Weinhold, C., Seidler, U. E., Colgan, S. P., et al. (2008) · The FASEB Journal · doi:10.1096/fj.08-110221 · Cited by 89 · see citing works
Preclinical evaluation of YC-1, a HIF inhibitor, for the prevention of tumor spreading
Shin, D. H., Kim, J.-H., Jung, Y.-J., Kim, K.-E., Jeong, J. M., Chun, Y.-S., & Park, J.-W. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.03.026 · Cited by 83 · see citing works
Interpretation of ileal biopsies: morphological features in normal and diseased mucosa
Cuvelier, C. A., Demetter, P., Mielants, H., VEYS, E. M., & Vos, M. D. (2001) · Histopathology · doi:10.1046/j.1365-2559.2001.01070.x · Cited by 71 · see citing works
Analysis of enteropathy induced by tumour necrosis factor α
Garside, P., Bunce, C., Tomlinson, R. C., Nichols, B. L., & Mowat, A. M. (1993) · Cytokine · doi:10.1016/1043-4666(93)90020-6 · Cited by 70 · see citing works
Mimata, H., Nomura, T., Sato, F., & Yamasaki, M. (2007) · Oncology Reports · doi:10.3892/or.18.5.1145 · Cited by 69 · see citing works
Piguet, P. F., Vesin, C., Donati, Y. R. A., & Barazzone‐Argiroffo, C. (1999) · PubMed · Cited by 68 · see citing works
Bang, S., Jeong, E.-J., Kim, I.-K., Jung, Y., & Kim, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006620200 · Cited by 59 · see citing works
Fries, W., Muja, C., Crisafulli, C., Costantino, G., Longo, G., Cuzzocrea, S., & Mazzon, E. (2008) · International Journal of Medical Sciences · doi:10.7150/ijms.5.169 · Cited by 56 · see citing works
Systemic and local evidence of increased Fas-mediated apoptosis in ulcerative colitis
Yukawa, M., Iizuka, M., Horie, Y., Yoneyama, K., Shirasaka, T., Itou, H., Komatsu, M., Fukushima, T., & Watanabe, S. (2001) · International Journal of Colorectal Disease · doi:10.1007/s003840100340 · Cited by 45 · see citing works
Regulation of intestinal epithelial gene expression in hypoxia
Taylor, C. T. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.761_12.x · Cited by 25 · see citing works
New Drugs Target Hypoxia Response in Tumors
Garber, K. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji261 · Cited by 22 · see citing works
Christer, J. F., Yacoub, M. H., & Brand, N. J. (1998) · Analytical Biochemistry · doi:10.1006/abio.1997.2505 · Cited by 1 · see citing works
Short peptides sensitize target cells to CTL specific for the MHC class Ib molecule, H2-M3
Dabhi, V. M., & Fischer Lindahl, K. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199811)28:11
Flagged first, then by citations
2 of the 56 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kelly, C. J., Zheng, L., Campbell, E. L., Saeedi, B., Scholz, C. C., Bayless, A. J., Wilson, K. E., Glover, L. E., Kominsky, D. J., Magnuson, A., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.03.005 · Cited by 1,716 · see citing works
Regulation of Immunity and Inflammation by Hypoxia in Immunological Niches
Taylor, C. T., & Colgan, S. P. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.103 · Cited by 713 · see citing works
Redox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377 · see citing works
McNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234 · see citing works
Regulation of the Hypoxia-Inducible Factor (HIF) by Pro-Inflammatory Cytokines
Malkov, M. I., Lee, C. T., & Taylor, C. T. (2021) · Cells · doi:10.3390/cells10092340 · Cited by 185 · see citing works
The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS
Mukandala, G., Tynan, R., Lanigan, S. M., & O'Connor, J. J. (2016) · Brain Sciences · doi:10.3390/brainsci6010006 · Cited by 170 · see citing works
Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction
Fricker, M., Goggins, B. J., Mateer, S. W., Jones, B., Kim, R., Gellatly, S. L., Jarnicki, A., Powell, N., Oliver, B. G. G., Radford‐Smith, G. L., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.94040 · Cited by 169 · see citing works
Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight Polymers
Shen, W., Wang, Q., Shen, Y., Gao, X., Li, L., Yan, Y., Wang, H., & Cheng, Y. (2018) · ACS Central Science · doi:10.1021/acscentsci.8b00363 · Cited by 169 · see citing works
Rabinowitz, M. H. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400386j · Cited by 165 · see citing works
Hypoxia and Innate Immunity: Keeping Up with the HIFsters
Colgan, S. P., Furuta, G. T., & Taylor, C. T. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-100819-121537 · Cited by 160 · see citing works
Fundamental role for HIF-1α in constitutive expression of human β defensin-1
Kelly, C. J., Glover, L. E., Campbell, E. L., Kominsky, D., Ehrentraut, S., Bowers, B., Bayless, A. J., Saeedi, B. J., & Colgan, S. P. (2013) · Mucosal Immunology · doi:10.1038/mi.2013.6 · Cited by 131 · see citing works
Tang, Y., Wang, D., Wang, Y., Huang, A., & Xu, W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1073971 · Cited by 126 · see citing works
Liu, S., Yu, H., Li, P., Wang, C., Liu, G., Zhang, X., ZHANG, C., Qi, M., & Ji, H. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.07.001 · Cited by 125 · see citing works
Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD
Welden, S. V., Selfridge, A. C., & Hindryckx, P. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.101 · Cited by 124 · see citing works
Self-citationProlyl 4‐hydroxylases, master regulators of the hypoxia response
Myllyharju, J. (2013) · Acta Physiologica · doi:10.1111/apha.12096 · Cited by 118 · see citing works
Hams, E., Saunders, S. P., Cummins, E. P., O'Connor, A., Tambuwala, M. T., Gallagher, W. M., Byrne, A., Campos-Torres, A., Moynagh, P. M., Jobin, C., et al. (2011) · Shock · doi:10.1097/shk.0b013e318225ad7e · Cited by 106 · see citing works
Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function
Manresa, M. C., & Taylor, C. T. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.02.004 · Cited by 106 · see citing works
Zhdanov, A. V., Okkelman, I. A., Collins, F. W. J., Melgar, S., & Papkovsky, D. B. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.06.016 · Cited by 101 · see citing works
Chassin, C., Hempel, C., Stockinger, S., Dupont, A., Kübler, J. F., Wedemeyer, J., Vandewalle, A., & Hornef, M. W. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201201298 · Cited by 87 · see citing works
Kim, Y.-E., Lee, M., Gu, H., Kim, J., Jeong, S., Yeo, S., Lee, Y. J., Im, S., Sung, Y., Kim, H. J., et al. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.033241 · Cited by 82 · see citing works
Tambuwala, M. M., Manresa, M. C., Cummins, E. P., Aversa, V., Coulter, I. S., & Taylor, C. T. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.09.022 · Cited by 69 · see citing works
Hypoxia-inducible factor 1 in autoimmune diseases
Deng, W., Feng, X., Li, X., Wang, D., & Sun, L. (2016) · Cellular Immunology · doi:10.1016/j.cellimm.2016.04.001 · Cited by 69 · see citing works
Schley, G., Klanke, B., Kalucka, J. M., Schatz, V., Daniel, C., Mayer, M., Goppelt‐Struebe, M., i, M. H., Þorsteinsdóttir, M., Pálsson, R., et al. (2019) · Kidney International · doi:10.1016/j.kint.2019.02.016 · Cited by 62 · see citing works
Hypoxia-sensitive pathways in inflammation-driven fibrosis
Manresa, M. C., Godson, C., & Taylor, C. T. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00349.2014 · Cited by 61 · see citing works
The hypoxia-inducible factor (HIF) couples immunity with metabolism
Halligan, D. N., Murphy, S. J. E., & Taylor, C. T. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.09.004 · Cited by 58 · see citing works
Xiao, Z., Sperl, B., Ullrich, A., & Knyazev, P. G. (2014) · Oncotarget · doi:10.18632/oncotarget.2657 · Cited by 55 · see citing works
Sun, M., He, C. H., Wu, W. H., Zhou, G., Liu, F., Cong, Y., & Liu, Z. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12896 · Cited by 54 · see citing works
FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications
Marín‐Rubio, J. L., Vela‐Martín, L., Fernández‐Piqueras, J., & Villa‐Morales, M. (2019) · Cancers · doi:10.3390/cancers11101462 · Cited by 52 · see citing works
Metabolic regulation of intestinal epithelial barrier during inflammation
Colgan, S. P., Curtis, V. F., Lanis, J. M., & Glover, L. E. (2014) · Tissue Barriers · doi:10.4161/21688362.2014.970936 · Cited by 49 · see citing works
FADD as a key molecular player in cancer progression
Liu, Y., Li, X., Zhou, X., Wang, J., & Ao, X. (2022) · Molecular Medicine · doi:10.1186/s10020-022-00560-y · Cited by 44 · see citing works
Hydroxylases as therapeutic targets in inflammatory bowel disease
Cummins, E. P., Doherty, G. A., & Taylor, C. T. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.9 · Cited by 44 · see citing works
Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis
Steiner, C. A., Cartwright, I. M., Taylor, C. T., & Colgan, S. P. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00227.2022 · Cited by 42 · see citing works
Yin, J., Ni, B., Liao, W.-G., & Gao, Y. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25974 · Cited by 42 · see citing works
Hypoxia‐sensitive pathways in intestinal inflammation
Brown, E., & Taylor, C. T. (2017) · The Journal of Physiology · doi:10.1113/jp274350 · Cited by 40 · see citing works
Low doses of Celecoxib attenuate gut barrier failure during experimental peritonitis
Short, S. S., Wang, J., Castle, S. L., Fernández, G. E., Smiley, N., Zobel, M. J., Pontarelli, E. M., Papillon, S. C., Grishin, A., & Ford, H. R. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.119 · Cited by 38 · see citing works
Welden, S. V., Vos, M. D., Wielockx, B., Tavernier, S. J., Dullaers, M., Neyt, S., Descamps, B., Devisscher, L., Devriese, S., den Bossche, L. V., et al. (2016) · The Journal of Pathology · doi:10.1002/path.4861 · Cited by 36 · see citing works
Self-citationCellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation
Ranjan, K., & Pathak, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063228 · Cited by 35 · see citing works
Muramyl dipeptide responsive pathways in Crohn’s disease: from NOD2 and beyond
Salem, M. A., Seidelin, J. B., Rogler, G., & Nielsen, O. H. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1246-4 · Cited by 35 · see citing works
Immunologic Consequences of Hypoxia during Critical Illness
Kiers, H. D., Scheffer, G., van der Hoeven, J. G., Eltzschig, H. K., Pickkers, P., & Kox, M. (2016) · Anesthesiology · doi:10.1097/aln.0000000000001163 · Cited by 35 · see citing works
Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer
Cui, X., Tinholt, M., Stavik, B., Dahm, A. E. A., Kanse, S. M., Jin, Y., Seidl, S., Sahlberg, K. K., Iversen, N., Skretting, G., et al. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13206 · Cited by 31 · see citing works
Luo, H., Du, M., Lin, Z., Zhang, L., Ma, L., Wang, H., Yu, W. Y., Lv, Y., Lu, J., Pi, Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077523 · Cited by 31 · see citing works
Hechinger, A.-K., Maas‐Bauer, K., Dürr, C., Leonhardt, F., Prinz, G., Marks, R., Gerlach, U. V., Hofmann, M., Fisch, P., Finke, J., et al. (2012) · Haematologica · doi:10.3324/haematol.2012.065789 · Cited by 30 · see citing works
Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner
Fitzpatrick, S. F., Fábián, Z., Schaible, B., Lenihan, C. R., Schwarzl, T., Rodríguez, J., Zheng, X., Li, Z., Tambuwala, M. M., Higgins, D. G., et al. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.04.085 · Cited by 30 · see citing works
Welden, S. V., Laukens, D., Ferdinande, L., Vos, M. D., & Hindryckx, P. (2013) · Journal of Inflammation · doi:10.1186/1476-9255-10-36 · Cited by 28 · see citing works
Self-citationHypoxia inhibits TNF-α-induced TSLP expression in keratinocytes
Tashiro, N., Segawa, R., Tobita, R., Asakawa, S., Mizuno, N., Hiratsuka, M., & Hirasawa, N. (2019) · PLoS ONE · doi:10.1371/journal.pone.0224705 · Cited by 26 · see citing works
Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand–Induced Apoptosis and Lung Injury in Mice
Nagamine, Y., Tojo, K., Yazawa, T., Takaki, S., Baba, Y., Goto, T., & Kurahashi, K. (2016) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2015-0266oc · Cited by 25 · see citing works
Manresa, M. C., Smith, L., Casals‐Diaz, L., Fagundes, R. R., Brown, E., Radhakrishnan, P., Murphy, S. J., Crifò, B., Strowitzki, M. J., Halligan, D. N., et al. (2018) · Allergy · doi:10.1111/all.13655 · Cited by 25 · see citing works
Implications of Protein Post-Translational Modifications in IBD
Ehrentraut, S., & Colgan, S. P. (2012) · Inflammatory Bowel Diseases · doi:10.1002/ibd.22859 · Cited by 24 · see citing works
Lombardi, F., Augello, F. R., Palumbo, P., Bonfili, L., Artone, S., Altamura, S., Sheldon, J. M., Latella, G., Cifone, M. G., Eleuteri, A. M., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098134 · Cited by 22 · see citing works
High protein intake promotes the adaptation to chronic hypoxia in zebrafish (Danio rerio)
Ma, Q., Wang, X., Li, L., Qiao, F., Zhang, M., & Du, Z. (2021) · Aquaculture · doi:10.1016/j.aquaculture.2021.736356 · Cited by 18 · see citing works
Gojković, M., Cunha, P. P., Darmasaputra, G., Barbieri, L., Rundqvist, H., Veliça, P., & Johnson, R. S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.633586 · Cited by 17 · see citing works
microRNA-98 mediated microvascular hyperpermeability during burn shock phase via inhibiting FIH-1
Hu, D., Yu, Y., Wang, C., Li, D., Tai, Y., & Fang, L. (2015) · European journal of medical research · doi:10.1186/s40001-015-0141-5 · Cited by 16 · see citing works
Redox regulation of immunity and the role of small molecular weight thiols
Ghezzi, P. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102001 · Cited by 16 · see citing works
Targeting hypoxia in inflammatory bowel disease
Colgan, S. P. (2015) · Journal of Investigative Medicine · doi:10.1097/jim.0000000000000218 · Cited by 16 · see citing works
Oxygen regulates molecular mechanisms of cancer progression and metastasis
Gupta, K., Madan, E., Sayyid, M. M., Arias‐Pulido, H., Moreno, E., Kuppusamy, P., & Gogna, R. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9464-2 · Cited by 15 · see citing works
Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease
Lun, J., Zhang, H., Guo, J., Yu, M., & Fang, J. S. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1045997 · Cited by 14 · see citing works
Halligan, D. N., Khan, M. N., Brown, E., Rowan, C. R., Coulter, I. S., Doherty, G. A., Tambuwala, M. M., & Taylor, C. T. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00049.2019 · Cited by 14 · see citing works
Devisscher, L., Hindryckx, P., Olievier, K., Peeters, H., Vos, M. D., & Laukens, D. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.11.031 · Cited by 14 · see citing works
Self-citationNovel development in extraintestinal manifestations and spondylarthropathy
Vos, M. D., Hindryckx, P., & Laukens, D. (2011) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/s1521-6918(11)70006-3 · Cited by 12 · see citing works
Self-citationHabryka, A., Gogler‐Pigłowska, A., Sojka, D. R., Kryj, M., Krawczyk, Z., & Ścieglińska, D. (2015) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2015.07.004 · Cited by 10 · see citing works
Prolyl Hydroxylase Inhibition Mitigates Pouchitis
Harnoss, J. M., Gebhardt, J. M., Radhakrishnan, P., Leowardi, C., Burmeister, J., Halligan, D. N., Yuan, S., Kennel, K. B., Strowitzki, M. J., Schaible, A., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz218 · Cited by 8 · see citing works
Palaniyandi, S., Kumari, R., Radhakrishnan, S. V., Strattan, E., Hakim, N., Munker, R., Kesler, M., & Hildebrandt, G. C. (2020) · Transplantation · doi:10.1097/tp.0000000000003383 · Cited by 8 · see citing works
The role of glycolysis in inflammation
Dehantschutter, E. T., & Taylor, C. T. (2026) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00113.2026 · Cited by 7 · see citing works
Galan, C. D., Vos, M. D., Hindryckx, P., Laukens, D., & Welden, S. V. (2021) · Biology · doi:10.3390/biology10090887 · Cited by 7 · see citing works
Self-citationLactic Acid Reduces LPS-Induced TNF-α and IL-6 mRNA Levels Through Decreasing IKBα Phosphorylation
Guangyong, X., Jiang, J.-Q., Wang, M., Li, L., Su, J., & Xiao-ming, R. E. N. (2013) · Journal of Integrative Agriculture · doi:10.1016/s2095-3119(13)60486-4 · Cited by 6 · see citing works
Liu, J., Jiu-zhou, X. U. E., Zhi-ning, Z. H. U., Hu, G., & Xiao-ming, R. E. N. (2011) · Agricultural Sciences in China · doi:10.1016/s1671-2927(11)60081-3 · Cited by 6 · see citing works
Hindryckx, P., Laukens, D., & Vos, M. D. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21589 · Cited by 5 · see citing works
Self-citationPinto-Cardoso, R., Bessa-Andrês, C., Pereira-Costa, F., Neiva, R., Martins-Ferreira, R., Leal, B., Catelas, D. N., Vilaça, A., Oliveira, A., Pelletier, J., et al. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00190 · Cited by 4 · see citing works
NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION
Caria, C. R. E. P., Moscato, C. H., TOMÉ, R. B. G., Pedrazzoli, J., Ribeiro, M. L., & Gambero, A. (2014) · Arquivos de Gastroenterologia · doi:10.1590/s0004-28032014000400007 · Cited by 4 · see citing works
McFarlin, B. K., Deemer, S. E., & Bridgeman, E. A. (2024) · Biomedicines · doi:10.3390/biomedicines12102386 · Cited by 3 · see citing works
Du, H., Ran, J., Wang, C., Cao, Y., Kong, C., Ma, H., Liu, T., Liu, M., Li, P., Huang, Y., et al. (2026) · Journal of Fish Diseases · doi:10.1111/jfd.70217 · Cited by 2 · see citing works
Zhang, L., Du, Y., Dong, X., Gao, R., Wang, W., Li, X., Xiao, G., Liu, S., Xue, Y., Tassanbiyeva, A., et al. (2026) · Advanced Healthcare Materials · doi:10.1002/adhm.71639 · Cited by 1 · see citing works
The role of HIF-1α in innate immune mechanisms and autoimmunity: A double-edged sword
Chapple, M. L., Zaldumbide, A., & Fagundes, R. R. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111429
- Authors
- Hindryckx, P., De Vos, M., Jacques, P., Ferdinande, L., Peeters, H., Olievier, K., Bogaert, S., Brinkman, B., Vandenabeele, P., Elewaut, D., & Laukens, D.
- Affiliations
- Ghent University (BE)
- Department of Gastroenterology, Ghent University , Zwijnaarde ,
- Vlaams Instituut voor Biotechnologie (BE)
- Corresponding author
- Hindryckx, Pieter
- Peeters, Harald
- Olievier, Kim
- Bogaert, Sara
- Laukens, Debby
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-11
- Volume
- 185
- Issue
- 10
- Pages
- 6306-6316
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2098087741
- Cited by
- 73
- References
- 56
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 7 · 2014: 4 · 2013: 10 · 2012: 5
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- HIF-1, HIF-1α, FADD, TNF-α, intestinal epithelial barrier, intestinal epithelial cell apoptosis, death receptor signaling, inflammatory bowel disease, terminal ileitis, hypoxia, intestinal inflammation
- MeSH terms
- Amino Acids, Dicarboxylic, Animals, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Humans, Mixed Function Oxygenases, Ileitis, Immunohistochemistry, Intestinal Mucosa, Mice, Inbred C57BL, Mice, Mutant Strains, Promoter Regions, Genetic, Tumor Necrosis Factor-alpha, Blotting, Western, Cell Hypoxia, Immunity, Mucosal, Reverse Transcriptase Polymerase Chain Reaction, Chromatin Immunoprecipitation, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Fas-Associated Death Domain Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
