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

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 l...

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Bibliographische Detailangaben
Hauptverfasser: Thiele, Wilko (VerfasserIn) , Rothley, Melanie (VerfasserIn) , Kuch, Vanessa (VerfasserIn) , Quagliata, Luca (VerfasserIn) , Sleeman, Jonathan P. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 13, 2012
In: Blood
Year: 2012, Jahrgang: 120, Heft: 9, Pages: 1899-1907
ISSN:1528-0020
DOI:10.1182/blood-2011-09-376657
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1182/blood-2011-09-376657
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Verfasserangaben:Wilko Thiele, Jaya Krishnan, Melanie Rothley, Debra Weih, Diana Plaumann, Vanessa Kuch, Luca Quagliata, Herbert A. Weich, and Jonathan P. Sleeman
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 18.04.2018
Beschreibung:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2011-09-376657

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