Thumbnail Image
Publication

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

Thiele, Wilko
; 
Krishnan, Jaya
; 
Rothley, Melanie
; 
Weih, Debra
; 
Plaumann, Diana
; 
Kuch, Vanessa
; 
Quagliata, Luca
; 
Weich, Herbert A
; 
Sleeman, Jonathan P
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2012-08-30
Submitted date
Show all metadata
Files
Thumbnail Image
original manuscript
Adobe PDF, 319.14 KB
Thumbnail Image
figure 5
JPEG, 394.09 KB
Thumbnail Image
figure 4
JPEG, 182.88 KB
Thumbnail Image
supplemental data and figures
Adobe PDF, 4.7 MB
Thumbnail Image
figure 1
JPEG, 388.8 KB
Other Titles
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.
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
Affiliation
Universität Heidelberg, Medizinische Fakultät Mannheim, Mannheim, Germany;
Publisher
Journal
Blood
URI
http://hdl.handle.net/10033/245952
DOI
10.1182/blood-2011-09-376657
PubMed ID
22797697
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1528-0020
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Archived with thanks to Blood
Collections
Publications of Dept. Gene Regulation and Differentiation (RDIF)