The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
HIF-1–dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia
Open accessAbstract
Extracellular adenosine (Ado) has been implicated as central signaling molecule during conditions of limited oxygen availability (hypoxia), regulating physiologic outcomes as diverse as vascular leak, leukocyte activation, and accumulation. Presently, the molecular mechanisms that elevate extracellular Ado during hypoxia are unclear. In the present study, we pursued the hypothesis that diminished uptake of Ado effectively enhances extracellular Ado signaling. Initial studies indicated that the half-life of Ado was increased by as much as fivefold after exposure of endothelia to hypoxia. Examination of expressional levels of the equilibrative nucleoside transporter (ENT)1 and ENT2 revealed a transcriptionally dependent decrease in mRNA, protein, and function in endothelia and epithelia. Examination of the ENT1 promoter identified a hypoxia inducible factor 1 (HIF-1)–dependent repression of ENT1 during hypoxia. Using in vitro and in vivo models of Ado signaling, we revealed that decreased Ado uptake promotes vascular barrier and dampens neutrophil tissue accumulation during hypoxia. Moreover, epithelial Hif1α mutant animals displayed increased epithelial ENT1 expression. Together, these results identify transcriptional repression of ENT as an innate mechanism to elevate extracellular Ado during hypoxia.
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Cites
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Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · cited 1×
“Given the temporal and robust hypoxia response observed in the repression of ENT1, a candidate regulator was HIF-1, a heterodimeric transcription factor whose activation is dependent on stabilization of an O2-dependent degradation domain (31).”
BackgroundOhta, A., & Sitkovsky, M. (2001) · Nature · doi:10.1038/414916a · Cited by 1,334
HMEC-1: Establishment of an Immortalized Human Microvascular Endothelial Cell Line
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Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
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The equilibrative nucleoside transporter family, SLC29
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Molecular Approach to Adenosine Receptors: Receptor-Mediated Mechanisms of Tissue Protection
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Self-citation
Cited by
Eltzschig, H. K., & Carmeliet, P. (2011) · New England Journal of Medicine · doi:10.1056/nejmra0910283 · Cited by 2,061
Self-citationBours, M. J. L., Swennen, E. L. R., Di Virgilio, F., Cronstein, B. N., & Dagnelie, P. C. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.04.013 · Cited by 1,030
Environmental triggers in IBD: a review of progress and evidence
Ananthakrishnan, A. N., Bernstein, C. N., Iliopoulos, D., Macpherson, A., Neurath, M. F., Ali, R. A. R., Vavricka, S. R., & Fiocchi, C. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.136 · Cited by 948
The adenosine pathway in immuno-oncology
Allard, B., Allard, D., Buisseret, L., & Stagg, J. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0382-2 · Cited by 586
Farrell, J. J., Elsaleh, H., Garcia, M., Lai, R., Ammar, A., Regine, W. F., Abrams, R., Benson, A. B., Macdonald, J., Cass, C. E., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2008.09.067 · Cited by 458
Metadata
- Authors
- Eltzschig, H. K., Abdulla, P., Hoffman, E., Hamilton, K. E., Daniels, D., Schönfeld, C., Löffler, M., Reyes, G., Duszenko, M., Karhausen, J., Robinson, A., Westerman, K. A., Coe, I. R., & Colgan, S. P.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-12-05
- Volume
- 202
- Issue
- 11
- Pages
- 1493-1505
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2141035582
- Cited by
- 351
- References
- 42
- FWCI
- 7.97
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Eltzschig, H. K., Abdulla, P., Hoffman, E., Hamilton, K. E., Daniels, D., Schönfeld, C., Löffler, M., Reyes, G., Duszenko, M., Karhausen, J., Robinson, A., Westerman, K. A., Coe, I. R., & Colgan, S. P. (2005). HIF-1–dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20050177
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