Enforced expression of KDR receptor promotes proliferation, survival and megakaryocytic differentiation of TF1 progenitor cell line View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-01

AUTHORS

S Coppola, L Narciso, T Feccia, D Bonci, L Calabrò, O Morsilli, M Gabbianelli, R De Maria, U Testa, C Peschle

ABSTRACT

Vascular endothelial growth factor (VEGF) receptor-2/kinase insert domain-containing receptor (KDR) is expressed in primitive hematopoietic cells, in megakaryocytes and platelets. In primitive hematopoiesis KDR mediates cell survival via autocrine VEGF, while its effect on cell growth and differentiation has not been elucidated. We induced enforced KDR expression in the granulocyte macrophage-colony-stimulating factor (GM-CSF)-dependent TF1 progenitor cell line (TF1-KDR), treated the cells with VEGF and analyzed their response. In GM-CSF-deprived cells, VEGF induces cell proliferation and protection against apoptosis, followed by enhanced expression of megakaryocytic (MK) markers. Combined with GM-CSF, VEGF induces a mild proliferative stimulus, followed by cell adherence, accumulation in G0/G1, massive MK differentiation and Fas-mediated apoptosis. Accordingly, we observed that MK-differentiating cells, derived from hematopoietic progenitors, produce VEGF, express KDR, inhibition of which reduces MK differentiation, indicating a key role of KDR in megakaryopoiesis. In conclusion, TF1-KDR cells provide a reliable model to investigate the biochemical and molecular mechanisms underlying hematopoietic progenitor proliferation, survival and MK differentiation. More... »

PAGES

4401698

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cdd.4401698

DOI

http://dx.doi.org/10.1038/sj.cdd.4401698

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032242869

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15962006


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