VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis

• Verfasst von: Thiele, Wilko [VerfasserIn]
• Verfasst von: Rothley, Melanie [VerfasserIn]
• Verfasst von: Kuch, Vanessa [VerfasserIn]
• Verfasst von: Quagliata, Luca [VerfasserIn]
• Verfasst von: Sleeman, Jonathan P. [VerfasserIn]
• Titel: VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis
• Verf.angabe: Wilko Thiele, Jaya Krishnan, Melanie Rothley, Debra Weih, Diana Plaumann, Vanessa Kuch, Luca Quagliata, Herbert A. Weich, and Jonathan P. Sleeman
• E-Jahr: 2012
• Jahr: July 13, 2012
• Umfang: 9 S.
• Fussnoten: Gesehen am 18.04.2018
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2012
• Band/Heft Quelle: 120(2012), 9, Seite 1899-1907
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2011-09-376657
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cell-lines
• Sach-SW: growth-factors
• Sach-SW: in-vivo
• Sach-SW: induced lymphangiogenesis
• Sach-SW: molecular-mechanisms
• Sach-SW: platelets
• Sach-SW: progenitor
• Sach-SW: receptor
• Sach-SW: regeneration
• Sach-SW: thrombopoietin
• K10plus-PPN: 1572141697

Abstract

VEGFR-3 is a transmembrane receptor tyrosine kinase that is activated by its ligands VEGF-C and VEGF-D. Although VEGFR-3 has been linked primarily to the regulation of lymphangiogenesis, in the present study, we demonstrate a role for VEGFR-3 in megakaryopoiesis. Using a human erythroleukemia cell line and primary murine BM cells, we show that VEGFR-3 is expressed on megakaryocytic progenitor cells through to the pro-megakaryoblast stage. Functionally, specific activation of VEGFR-3 impaired the transition to polyploidy of CD41(+) cells in primary BM cultures. Blockade of VEGFR-3 promoted endoreplication consistently. In vivo, long-term activation or blockade of VEGFR-3 did not affect steady-state murine megakaryopoiesis or platelet counts significantly. However, activation of VEGFR-3 in sublethally irradiated mice resulted in significantly elevated numbers of CD41(+) cells in the BM and a significant increase in diploid CD41(+) cells, whereas the number of polyploid CD41(+) cells was reduced significantly. Moreover, activation of VEGFR-3 increased platelet counts in thrombopoietin-treated mice significantly and modulated 5-fluorouracil-induced thrombocytosis strongly, suggesting a regulatory role for VEGFR-3 in megakaryopoiesis.