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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5352-5360. Prepublished online as a Blood First Edition Paper on March 27, 2009; DOI 10.1182/blood-2008-08-173773.
VASCULAR BIOLOGY Inhibition of endothelial progenitor cell differentiation by VEGI1 Department of Pathology, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, PA; and 2 College of Pharmacy, Nankai University, Tianjin, China
Endothelial progenitor cells (EPCs) play a critical role in postnatal and tumor vasculogenesis. Vascular endothelial growth inhibitor (VEGI; TNFSF15) has been shown to inhibit endothelial cell proliferation by inducing apoptosis. We report here that VEGI inhibits the differentiation of EPCs from mouse bone marrow–derived Sca1+ mononuclear cells. Analysis of EPC markers indicates a significant decline of the expression of endothelial cell markers, but not stem cell markers, on VEGI-treated cells. Consistently, the VEGI-treated cells exhibit a decreased capability to adhere, migrate, and form capillary-like structures on Matrigel. In addition, VEGI induces apoptosis of differentiated EPCs but not early-stage EPCs. When treated with VEGI, an increase of phospho-Erk and a decrease of phospho-Akt are detected in early-stage EPCs, whereas activation of nuclear factor-
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| Copyright © 2009 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||