The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs
Abstract
Cellular responses to oxygen are increasingly recognized as critical in normal development and physiology, and are implicated in pathological processes. Many of these responses are mediated by the transcription factors HIF‐1 and HIF‐2. Their regulation occurs through oxygen‐dependent proteolysis of the alpha subunits HIF‐1α and HIF‐2α, respectively. Both are stabilized in cell lines exposed to hypoxia, and recently HIF‐1α was reported to be widely expressed in vivo . In contrast, regulation and sites of HIF‐2α expression in vivo are unknown, although a specific role in endothelium was suggested. We therefore analyzed HIF‐2α expression in control and hypoxic rats. Although HIF‐2α was not detectable under baseline conditions, marked hypoxic induction occurred in all organs investigated, including brain, heart, lung, kidney, liver, pancreas, and intestine. Time course and amplitude of induction varied between organs. Immunohistochemistry revealed nuclear accumulation in distinct cell populations of each tissue, which were exclusively non‐parenchymal in some organs (kidney, pancreas, and brain), predominately parenchymal in others (liver and intestine) or equally distributed (myocardium). These data indicate that HIF‐2 plays an important role in the transcriptional response to hypoxia in vivo , which is not confined to the vasculature and is complementary to rather than redundant with HIF‐1.
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Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
Self-citationThe 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
Self-citationHIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
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
Wenger, R. H. (2002) · The FASEB Journal · doi:10.1096/fj.01-0944rev · Cited by 1,135
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Self-citationHIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796
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Cited by
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
Self-citationRole of hypoxia in cancer therapy by regulating the tumor microenvironment
Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1089-9 · Cited by 2,054
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
The impact of O2 availability on human cancer
Bertout, J. A., Patel, S. A., & Simon, M. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2540 · Cited by 1,365
Metadata
- Authors
- Wiesener, M. S., Jürgensen, J. S., Rosenberger, C., Scholze, C., Hörstrup, J. H., Warnecke, C., Mandriota, S., Bechmann, I., Frei, U. A., Pugh, C. W., Ratcliffe, P. J., Bachmann, S., Maxwell, P. H., & Eckardt, K.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2002-12-17
- Volume
- 17
- Issue
- 2
- Pages
- 271-273
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2136875815
- Cited by
- 740
- References
- 9
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wiesener, M. S., Jürgensen, J. S., Rosenberger, C., Scholze, C., Hörstrup, J. H., Warnecke, C., Mandriota, S., Bechmann, I., Frei, U. A., Pugh, C. W., Ratcliffe, P. J., Bachmann, S., Maxwell, P. H., & Eckardt, K. (2003). Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs. The FASEB Journal. https://doi.org/10.1096/fj.02-0445fje
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