The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium
Open accessAbstract
The flow-responsive transcription factor KLF2 is acquiring a leading role in the regulation of endothelial cell gene expression. A genome-wide microarray expression profiling is described employing lentivirus-mediated, 7-day overexpression of human KLF2 at levels observed under prolonged flow. KLF2 is not involved in lineage typing, as 42 endothelial-specific markers were unaffected. Rather, KLF2 generates a gene transcription profile (> 1000 genes) affecting key functional pathways such as cell migration, vasomotor function, inflammation, and hemostasis and induces a morphology change typical for shear exposure including stress fiber formation. Protein levels for thrombomodulin, endothelial nitric oxide synthase, and plasminogen activator inhibitor type-1 are altered to atheroprotective levels, even in the presence of the inflammatory cytokine TNF-α. KLF2 attenuates cell migration by affecting multiple genes including VEGFR2 and the potent antimigratory SEMA3F. The distribution of Weibel-Palade bodies in cultured cell populations is normalized at the single-cell level without interfering with their regulated, RalA-dependent release. In contrast, thrombin-induced release of Weibel-Palade bodies is significantly attenuated, consistent with the proposed role of VWF release at low–shear stress regions of the vasculature in atherosclerosis. These results establish that KLF2 acts as a central transcriptional switch point between the quiescent and activated states of the adult endothelial cell.
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Discovery of common and rare genetic risk variants for colorectal cancer
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Metadata
- Authors
- Dekker, R. J., Boon, R. A., Rondaij, M. G., Kragt, A., Volger, O. L., Elderkamp, Y. W., Meijers, J. C. M., Voorberg, J., Pannekoek, H., & Horrevoets, A. J. G.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-06-01
- Volume
- 107
- Issue
- 11
- Pages
- 4354-4363
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2147107152
- Cited by
- 353
- References
- 39
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dekker, R. J., Boon, R. A., Rondaij, M. G., Kragt, A., Volger, O. L., Elderkamp, Y. W., Meijers, J. C. M., Voorberg, J., Pannekoek, H., & Horrevoets, A. J. G. (2006). KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium. Blood. https://doi.org/10.1182/blood-2005-08-3465
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