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VEGFR-3 is expressed on megakaryocyte precursors in the murine bone marrow and plays a regulatory role in megakaryopoiesis.
- Source :
-
Blood [Blood] 2012 Aug 30; Vol. 120 (9), pp. 1899-907. Date of Electronic Publication: 2012 Jul 13. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Antimetabolites pharmacology
Blotting, Western
Bone Marrow Cells drug effects
Cell Differentiation drug effects
Cell Line, Tumor
Cells, Cultured
Fluorouracil pharmacology
Gene Expression
HEK293 Cells
Humans
Megakaryocyte Progenitor Cells drug effects
Megakaryocytes cytology
Megakaryocytes metabolism
Mice
Mice, Inbred C57BL
Phorbol Esters pharmacology
Platelet Count
Platelet Membrane Glycoprotein IIb metabolism
Ploidies
Reverse Transcriptase Polymerase Chain Reaction
Thrombopoietin pharmacology
Vascular Endothelial Growth Factor C pharmacology
Vascular Endothelial Growth Factor Receptor-3 genetics
Bone Marrow Cells metabolism
Megakaryocyte Progenitor Cells metabolism
Thrombopoiesis
Vascular Endothelial Growth Factor Receptor-3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 22797697
- Full Text :
- https://doi.org/10.1182/blood-2011-09-376657