The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Orphan nuclear receptor TR3/Nur77 regulates VEGF-A–induced angiogenesis through its transcriptional activity
Open accessAbstract
Vascular endothelial growth factor (VEGF)-A has essential roles in vasculogenesis and angiogenesis, but the downstream steps and mechanisms by which human VEGF-A acts are incompletely understood. We report here that human VEGF-A exerts much of its angiogenic activity by up-regulating the expression of TR3 (mouse homologue Nur77), an immediate-early response gene and orphan nuclear receptor transcription factor previously implicated in tumor cell, lymphocyte, and neuronal growth and apoptosis. Overexpression of TR3 in human umbilical vein endothelial cells (HUVECs) resulted in VEGF-A–independent proliferation, survival, and induction of several cell cycle genes, whereas expression of antisense TR3 abrogated the response to VEGF-A in these assays and also inhibited tube formation. Nur77 was highly expressed in several types of VEGF-A–dependent pathological angiogenesis in vivo. Also, using a novel endothelial cell-selective retroviral targeting system, overexpression of Nur77 DNA potently induced angiogenesis in the absence of exogenous VEGF-A, whereas Nur77 antisense strongly inhibited VEGF-A–induced angiogenesis. B16F1 melanoma growth and angiogenesis were greatly inhibited in Nur77−/− mice. Mechanistic studies with TR3/Nur77 mutants revealed that TR3/Nur77 exerted most of its effects on cultured HUVECs and its pro-angiogenic effects in vivo, through its transactivation and DNA binding domains (i.e., through transcriptional activity).
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Cites
Angiogenesis in cancer and other diseases
Carmeliet, P., & Jain, R. K. (2000) · Nature · doi:10.1038/35025220 · Cited by 9,070
Angiogenesis in cancer, vascular, rheumatoid and other disease
Folkman, J. (1995) · Nature Medicine · doi:10.1038/nm0195-27 · Cited by 7,627
Brown, L. F., Yeo, K. T., Berse, B., Yeo, T. K., Senger, D. R., Dvorak, H. F., & van de Water, L. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.5.1375 · Cited by 878
Self-citationDvorak, H. F., Nagy, J. A., Feng, D., Brown, L. F., & Dvorak, A. M. (1999) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-642-59953-8_6 · Cited by 743
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Cited by
Analysis of nanoparticle delivery to tumours
Wilhelm, S., Tavares, A. J., Dai, Q., Ohta, S., Audet, J., Dvorak, H. F., & Chan, W. C. W. (2016) · Nature Reviews Materials · doi:10.1038/natrevmats.2016.14 · Cited by 5,218
Self-citationOrphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis
Palumbo-Zerr, K., Zerr, P., Distler, A., Fliehr, J., Mancuso, R., Huang, J., Mielenz, D., Tomcik, M., Fürnrohr, B. G., Scholtysek, C., et al. (2015) · Nature Medicine · doi:10.1038/nm.3777 · Cited by 342
Rodríguez-Calvo, R., Tajes, M., & Vázquez-Carrera, M. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1279146 · Cited by 117
Murphy, E., & Crean, D. (2015) · Biomolecules · doi:10.3390/biom5031302 · Cited by 82
“NR4A1 transcriptional activity is both necessary and sufficient for VEGF-A-Induced proliferation and survival of cultured endothelial cells (ECs) and for angiogenesis in vivo, while depletion of NR4A2 expression attenuates VEGF-A-induced endothelial proliferation, migration and in vivo matrigel angiogenesis [67,68].”
BackgroundMelanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease
Mykicki, N., Herrmann, A. M., Schwab, N., Deenen, R., Sparwasser, T., Limmer, A., Wachsmuth, L., Klotz, L., Köhrer, K., Faber, C., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf8732 · Cited by 60
Metadata
- Authors
- Zeng, H., Qin, L., Zhao, D., Tan, X., Manseau, E. J., Van Hoang, M., Senger, D. R., Brown, L. F., Nagy, J. A., & Dvorak, H. F.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-03-06
- Volume
- 203
- Issue
- 3
- Pages
- 719-729
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2126018509
- Cited by
- 164
- References
- 4
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Zeng, H., Qin, L., Zhao, D., Tan, X., Manseau, E. J., Van Hoang, M., Senger, D. R., Brown, L. F., Nagy, J. A., & Dvorak, H. F. (2006). Orphan nuclear receptor TR3/Nur77 regulates VEGF-A–induced angiogenesis through its transcriptional activity. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20051523
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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