VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis.
dc.contributor.author | Thiele, Wilko | |
dc.contributor.author | Krishnan, Jaya | |
dc.contributor.author | Rothley, Melanie | |
dc.contributor.author | Weih, Debra | |
dc.contributor.author | Plaumann, Diana | |
dc.contributor.author | Kuch, Vanessa | |
dc.contributor.author | Quagliata, Luca | |
dc.contributor.author | Weich, Herbert A | |
dc.contributor.author | Sleeman, Jonathan P | |
dc.date.accessioned | 2012-09-26T14:24:10Z | |
dc.date.available | 2012-09-26T14:24:10Z | |
dc.date.issued | 2012-08-30 | |
dc.identifier.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 | en_GB |
dc.identifier.issn | 1528-0020 | |
dc.identifier.pmid | 22797697 | |
dc.identifier.doi | 10.1182/blood-2011-09-376657 | |
dc.identifier.uri | http://hdl.handle.net/10033/245952 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to Blood | en_GB |
dc.title | VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis. | en |
dc.type | Article | en |
dc.contributor.department | Universität Heidelberg, Medizinische Fakultät Mannheim, Mannheim, Germany; | en_GB |
dc.identifier.journal | Blood | en_GB |
refterms.dateFOA | 2018-06-12T17:24:21Z | |
html.description.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. |