The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis
Open accessAbstract
Mucosal epithelial cells are uniquely equipped to maintain barrier function even under adverse conditions. Previous studies have implicated hypoxia in mucosal tissue damage resulting from both acute and chronic inflammation. Given the importance of the transcriptional regulator hypoxia-inducible factor-1 (HIF-1) for adaptive hypoxia responses, we hypothesized that HIF-1 may serve as a barrier-protective element during mucosal inflammation. Initial studies of hapten-based murine colitis revealed extensive mucosal hypoxia and concomitant HIF-1 activation during colitis. To study this in more detail, we generated 2 mouse lines with intestinal epithelium–targeted expression of either mutant Hif1a (inability to form HIF-1) or mutant von Hippel-Lindau gene (Vhlh; constitutively active HIF-1). Studies of colitis in these mice revealed that decreased HIF-1 expression correlated with more severe clinical symptoms (mortality, weight loss, colon length), while increased HIF levels were protective in these parameters. Furthermore, colons with constitutive activation of HIF displayed increased expression levels of HIF-1–regulated barrier-protective genes (multidrug resistance gene-1, intestinal trefoil factor, CD73), resulting in attenuated loss of barrier during colitis in vivo. Taken together, these studies provide insight into tissue microenvironmental changes during model inflammatory bowel disease and identify HIF-1 as a critical factor for barrier protection during mucosal insult.
Overview
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
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“In addition, studies of active inflammation in mouse models of IBD have shown the intestinal epithelial cell to be a primary target for hypoxia13.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [13]
In the citing paper
“The same series of studies which identified inflammation-related hypoxia also showed that expression of HIF-1 is induced in the inflammatory lesions13.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [13]
In the citing paper
“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.”
From Hypoxia: an alarm signal during intestinal inflammation (2010) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Chen, L., Li, N., & Ye, H. (2012) · Hepatogastroenterology · doi:10.5754/hge12469 · Cited by 3,208
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
HIF-1α is essential for myeloid cell-mediated inflammation
Cramer, T., Yamanishi, Y., Clausen, B. E., Förster, I., Pawlinski, R., Mackman, N., Haase, V. H., Jaenisch, R., Corr, M., Nizet, V., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00154-5 · Cited by 2,046
Self-citationRegulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · cited 5×
“At day 7 after induction, both the wellcharacterized HIF-1–responsive gene product glucose transporter-1 (GLUT-1) (21) and 2 more recently characterized barrier-protective gene products, ITF and the MDR1 gene product P-glycoprotein”
InfluentialDer, S. D., Zhou, A., Williams, B. R. G., & Silverman, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15623 · Cited by 1,840
Hapten-Induced Model of Chronic Inflammation and Ulceration in the Rat Colon
Morris, G. P., Beck, P. L., Herridge, M. S., Depew, W. T., Szewczuk, M. R., & Wallace, J. L. (1989) · Gastroenterology · doi:10.1016/s0016-5085(89)80079-4 · Cited by 1,832
HIF‐1α is required for solid tumor formation and embryonic vascularization
Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579
Self-citation
Research works printed but not linked: 7
- Hauser, 1988, J. Lab. Clin. Med., 112, 68
- Comerford, 2002, Cancer Res., 62, 3387
- Evans, 2000, Cancer Res., 60, 2018
- Lee, 1998, Cancer Res., 58, 504
- 10.1042/0264-6021:3500307 · DOI
- Laughlin, 1996, J. Pharmacol. Exp. Ther., 277, 1049
- Zhang, 1997, Biotechniques., 22, 849
Cited by
Sorted by citations
Items 601–654 of 654
Smith, G. (2015) · Enlighten: Theses (The University of Glasgow)
Winning, S. (2010) · DuEPublico (University of Duisburg-Essen)
Functional Analysis of Trefoil Factors 1 and 3 in Tumorigenesis
Radiloff, D. R. (2009) · DukeSpace (Duke University)
Parameters of Experimental Colitis Receptors to Inflammatory Contribution of Adenosine A2B
Glover, L. E., Eltzschig, H. K., & MacManus, C. F. (2010)
Review The updated biology of hypoxia-inducible factor
Greer, S. N., Metcalf, J. L., Wang, Y., & Ohh, M. (2016)
ATP release from vascular endothelia occurs through connexin 43 and is attenuated during hypoxia
Tübingen, I., Direktor, Ä., & Unertl, K. E. (2009)
hypoxia: an alarm signal during intestinal
Taylor, C. T. (2010)
InflammationShifts in Immunity and
Kominsky, D. J., & Campbell, E. L. (2010)
Direktor, Ä., & Unertl, K. E. (2009)
Watanabe, S., Arimura, Y., Isshiki, H., Onodera, K., Nasuno, M., Yamashita, K., Adachi, Y., Shinomura, Y., Nagaishi, K., Fujimiya, M., et al. (2014)
Review Article In the eye of the storm: T cell behavior in the inflammatory microenvironment
Haas, R., Marelli‐Berg, F. M., & Mauro, C. (2013)
Mammalian O2 Sensing and Signalling
Chaplin, V. D., Barlow, A. N., & Knapp, M. J. (2017) · Royal Society of Chemistry eBooks · doi:10.1039/9781788012836-00219
Role of myeloid Hypoxia-Inducible Factor-1alpha in the tumor microenvironment
Doedens, A. L. (2008) · eScholarship (California Digital Library)
Developing models of the small intestine
Dosh, R. H. (2018) · Sheffield Hallam University · doi:10.7190/shu-thesis-00131
Selenium modulation of gut epithelial cell stress responses
Moore, A. N. (2017)
Chang, C., Liao, Y.-C., Huang, C., Lin, C.-M., Cheung, C. H. Y., Ruan, J., Yu, W.-H., Tsai, Y.-T., Juan, H., Huang, H., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-44154/v1
Jia, B., Tan, X.-Y., Liu, X., & Li, X. (2021) · Research Square · doi:10.21203/rs.3.rs-199959/v1
Torvund, M., Chakrabarti, J. L., & Zavros, Y. L. (2021) · Physiology in health and disease · doi:10.1007/978-3-030-67951-4_6
IMPACT OF HYPOXIA AND INFECTION ON THE MORPHOLOGY OF THETHYROID GLAND
Yaqubova, S. (2021) · Archiv Euromedica · doi:10.35630/2199-885x/2021/11/4.10
Elucidating the intestinal response to ischemia-reperfusion
Kip, A. M. (2022) · Research Publications (Maastricht University) · doi:10.26481/dis.20220210ak
CD73 alleviates GSDMD-mediated pyroptosis in spinal cord injury through PI3K/AKT/Foxo1 signalingPreprint
Xu, S., Shao, M., Ma, X., Jiang, J., Zhang, F., Xu, H., Zhu, W., & Lu, F. (2019) · doi:10.21203/rs.2.18409/v1
Faculty Opinions recommendation of Mechanisms of inflammation-driven bacterial dysbiosis in the gut.
Lin, H. C., & Lin, D. M. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.726669696.793561079
Weiss, M. J. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732587239.793577754
Studies on the mechanism of intestinal ischemic preconditioning
Varga, S. (2019) · SZTE Repository of Dissertations (University of Szeged) · doi:10.14232/phd.10334
Edwards, R. A., Witherspoon, M., Wang, K., Afrasiabi, K., Pham, T., Birnbaumer, L., & Lipkin, S. M. (2023) · doi:10.1158/0008-5472.c.6499140.v1
Cheng, M. I., Hong, L., Chen, B., Chin, S. C., Luthers, C. R., Bustillos, C. G., Sheikh, S. Z., & Su, M. A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.27.550746
Chugh, R. M., Bhanja, P., Zitter, R., Gunewardena, S., Badkul, R., & Saha, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.21.614209
Tian, Z., Huang, Y., Yang, Z., Yin, S., Zhang, F., & Yang, H. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.04.043
Association between gut actinobacteria and obstructive sleep apnoea severity in Japanese adults
Ueyama, M., Ohue‐Kitano, R., Kimura, I., & Kimura, H. (2025) · Respiratory Medicine · doi:10.1016/j.rmed.2025.108472
Fischer, N. (2014) · theses.fr (ABES) · doi:10.70675/7ecf88e2z7851z4354zb134z317e666a94cb
Injarabian, L. (2020) · theses.fr (ABES) · doi:10.70675/d505f876z0405z4419zbe01z07bf7a8dc156
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
Mulders, L., Pruijt, M., van Oostrom, J. M., van der Zanden, E. P., Neefjes‐Borst, A., Koelink, P. J., Wildenberg, M. E., de Jonge, W. J., Ridderikhof, M. L., van Hulst, R. A., et al. (2026) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjag065
Metabolic host-microbe crosstalk in stabilization of epithelial HIF
Dowdell, A. S., Roer, R. L., Bhagavatula, G., Cartwright, I. M., Cohen, R. H., Countess, J. A., Koch, S. D., Lee, J. S., Liu, L., Steiner, C. A., et al. (2026) · Microbiome · doi:10.1186/s40168-026-02431-8 · Cited by 1
Self-citationEnvironmental Pollutants and Neuroinflammation in Alzheimer’s Disease Progression
García-Núñez, A. (2026) · Journal of dementia and Alzheimer's disease · doi:10.3390/jdad3030033
Duan, X., Wang, D., Yang, B., Yan, H., Ma, H., Li, H., Wang, J., Gao, Q., Yu, S., Hou, X., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0355467
Cai, W., Wang, S., Hu, Y., Wang, P., Liang, X., Li, Z., & Wang, S. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107456
Zhang, B., Du, L., Zhang, K., Zhao, R., Yang, C., & Song, X. (2026) · Veterinary Sciences · doi:10.3390/vetsci13090874
Palenca, I., Sarnelli, G., & Esposito, G. (2026) · Biomedicines · doi:10.3390/biomedicines14092080
Dzhalilova, D. S., Fokichev, N., & Makarova, O. V. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1922856
Dietary Modulation of Intestinal Microbes Prolongs Survival in a Hirschsprung Disease Mouse Model
Tjaden, N. E. B., Liou, M. J., Sax, S. E., Lassoued, N., Lou, M., Schneider, S., Beigel, K., Eisenberg, J. D., Loeffler, E., Anderson, S. E., et al. (2026) · Gastroenterology · doi:10.1053/j.gastro.2026.09.007 · Cited by 3
Wei, L., 胡玉清, Lyu, Y., Qian, H., Qin, H., Wu, Y., & Zhang, X. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01656
Wu, Y., Lu, J., Mo, Y., Xu, Y., Yan, X., Yan, C., & Wang, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1998563
Tang, Y., XiaoDie, Z. H. O. U., Li, L., Zhan, C., & Yang, F. (2026) · Toxics · doi:10.3390/toxics14100899
Wu, M., Chen, L., Zhou, J., Huang, H., Chen, X., Wan, S., Xie, X., Zhou, M., & Zhang, Z. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1965973
Gut epithelial barriers as regulators of metabolite-driven immune responses
Tyagi, A., Tayal, R., Bhatt, D. N., Srivastava, S., Kumar, A., Kumar, A., & Kumar, V. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1959305
The role of ARNT in liver and myeloid cell function
Scott, C. H. (2013) · The Sydney eScholarship Repository (The University of Sydney)
Metadata
- Authors
- Karhausen, J., Furuta, G. T., Tomaszewski, J. E., Johnson, R. S., Colgan, S. P., & Haase, V. H.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Pennsylvania (US)
- University of California San Diego (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2004-10-15
- Volume
- 114
- Issue
- 8
- Pages
- 1098-1106
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC522241
- OpenAlex
- W1982920345
- Cited by
- 655
- References
- 60
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 25 · 2023: 43 · 2022: 29 · 2021: 35 · 2020: 41 · 2019: 37 · 2018: 32 · 2017: 38 · 2016: 46 · 2015: 40 · 2014: 29 · 2013: 44 · 2012: 37
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation of America
- Massachusetts Institute of Technology
- Crohn's and Colitis Foundation
- National Institutes of Health (DE13499, DK-50189, PO1 DE13499)
- National Heart, Lung, and Blood Institute (R01HL060569, HL-60569)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK002668, DK02668, R01DK050189, DK062060, R03DK062060, R37DK050189, R29DK050189, DK-50189)
- National Institute of Dental and Craniofacial Research (P01 DE 13499, P01DE013499)
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Digestive system and related health
- Keywords
- HIF-1, colitis, intestinal epithelium, mucosal barrier, intestinal hypoxia, inflammatory bowel disease, VHL, HIF1A, intestinal epithelial cells, TFF3, CD73, multidrug resistance gene 1, epithelial protection
- MeSH terms
- Animals, Carrier Proteins, Colitis, DNA-Binding Proteins, Gene Expression Regulation, Humans, Intestinal Mucosa, Mice, Inbred Strains, Mice, Transgenic, Nuclear Proteins, Recombination, Genetic, Transcription Factors, Cell Hypoxia, Gene Deletion, Genes, Reporter, Mice, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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
