The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Angiopoietin-2 functions as an autocrine protective factor in stressed endothelial cells
Abstract
Angiopoietin (Ang)-2, a context-dependent agonist/antagonist for the vascular-specific Tie2 receptor, is highly expressed by endothelial cells at sites of normal and pathologic angiogenesis. One prevailing model suggests that in these settings, Ang-2 acts as an autocrine Tie2 blocker, inhibiting the stabilizing influence of the Tie2 activator Ang-1, thereby promoting vascular remodeling. However, the effects of endogenous Ang-2 on cells that are actively producing it have not been studied in detail. Here, we demonstrate that Ang-2 expression is rapidly induced in endothelial cells by the transcription factor FOXO1 after inhibition of the phosphatidylinositol 3-kinase/Akt pathway. We employ RNAi and blocking antibodies to show that in this setting, Ang-2 unexpectedly functions as a Tie2 agonist, bolstering Akt activity so as to provide negative feedback on FOXO1-regulated transcription and apoptosis. In addition, we show that Ang-2, like Ang-1, activates Tie2/Akt signaling in vivo , thereby inhibiting the expression of FOXO1 target genes. Consistent with a role for Ang-2 as a Tie2 activator, we demonstrate that Ang-2 inhibits vascular leak. Our data suggests a model in which Ang-2 expression is induced in stressed endothelial cells, where it acts as an autocrine Tie2 agonist and protective factor.
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Fiedler, U., Reiss, Y., Scharpfenecker, M., Grunow, V., Koidl, S., Thurston, G., Gale, N. W., Witzenrath, M., Rosseau, S., Suttorp, N., et al. (2006) · Nature Medicine · doi:10.1038/nm1351 · Cited by 933
Self-citationKim, I., Kim, H. G., So, J.-N., Kim, J. H., Kwak, H. J., & Koh, G. Y. (2000) · Circulation Research · doi:10.1161/01.res.86.1.24 · Cited by 649
Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans
Parikh, S. M., Mammoto, T., Schultz, A., Yuan, H.-T., Christiani, D., Karumanchi, S. A., & Sukhatme, V. P. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030046 · Cited by 527
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The emerging roles of forkhead box (Fox) proteins in cancer
Myatt, S. S., & Lam, E. W. F. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2223 · Cited by 1,070
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Therapeutic targeting of the angiopoietin–TIE pathway
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Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology
Akwii, R. G., Sajib, M. S., Zahra, F. T., & Mikelis, C. M. (2019) · Cells · doi:10.3390/cells8050471 · Cited by 543
Metadata
- Authors
- Daly, C., Pasnikowski, E., Burova, E., Wong, V., Aldrich, T. H., Griffiths, J., Ioffe, E., Daly, T. J., Fandl, J. P., Papadopoulos, N., McDonald, D. M., Thurston, G., Yancopoulos, G. D., & Rudge, J. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-10-17
- Volume
- 103
- Issue
- 42
- Pages
- 15491-15496
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1978157267
- Cited by
- 251
- References
- 3
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- closed
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- Daly, C., Pasnikowski, E., Burova, E., Wong, V., Aldrich, T. H., Griffiths, J., Ioffe, E., Daly, T. J., Fandl, J. P., Papadopoulos, N., McDonald, D. M., Thurston, G., Yancopoulos, G. D., & Rudge, J. S. (2006). Angiopoietin-2 functions as an autocrine protective factor in stressed endothelial cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0607538103
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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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