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

2.50
HDL Handle:
http://hdl.handle.net/10033/245952
Title:
VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis.
Authors:
Thiele, Wilko; Krishnan, Jaya; Rothley, Melanie; Weih, Debra; Plaumann, Diana; Kuch, Vanessa; Quagliata, Luca; Weich, Herbert A; Sleeman, Jonathan P
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 promegakaryoblast 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.
Affiliation:
Universität Heidelberg, Medizinische Fakultät Mannheim, Mannheim, Germany;
Citation:
VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis. 2012, 120 (9):1899-907 Blood
Journal:
Blood
Issue Date:
30-Aug-2012
URI:
http://hdl.handle.net/10033/245952
DOI:
10.1182/blood-2011-09-376657
PubMed ID:
22797697
Type:
Article
Language:
en
ISSN:
1528-0020
Appears in Collections:
Publications of Dept. Gene Regulation and Differentiation (RDIF)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorThiele, Wilkoen_GB
dc.contributor.authorKrishnan, Jayaen_GB
dc.contributor.authorRothley, Melanieen_GB
dc.contributor.authorWeih, Debraen_GB
dc.contributor.authorPlaumann, Dianaen_GB
dc.contributor.authorKuch, Vanessaen_GB
dc.contributor.authorQuagliata, Lucaen_GB
dc.contributor.authorWeich, Herbert Aen_GB
dc.contributor.authorSleeman, Jonathan Pen_GB
dc.date.accessioned2012-09-26T14:24:10Z-
dc.date.available2012-09-26T14:24:10Z-
dc.date.issued2012-08-30-
dc.identifier.citationVEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis. 2012, 120 (9):1899-907 Blooden_GB
dc.identifier.issn1528-0020-
dc.identifier.pmid22797697-
dc.identifier.doi10.1182/blood-2011-09-376657-
dc.identifier.urihttp://hdl.handle.net/10033/245952-
dc.description.abstractVEGFR-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 promegakaryoblast 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Blooden_GB
dc.titleVEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis.en
dc.typeArticleen
dc.contributor.departmentUniversität Heidelberg, Medizinische Fakultät Mannheim, Mannheim, Germany;en_GB
dc.identifier.journalBlooden_GB

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